Enriched environment elevates expression of growth associated protein-43 in the substantia nigra of SAMP8 mice
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摘要
An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43(GAP-43) is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8(SAMP8) mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that m RNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.
An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43(GAP-43) is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8(SAMP8) mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that m RNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.
An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43(GAP-43) is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8(SAMP8) mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that m RNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.
引文
Aigner L,Caroni P(1993)Depletion of 43-k D growth-associated protein in primary sensory neurons leads to diminished formation and spreading of growth cones.J Cell Biol 123:417-429.
Baumgartel K,Mansuy IM(2012)Neural functions of calcineurin in synaptic plasticity and memory.Learn Mem 19:375-384.
Beauquis J,Roig P,De Nicola AF,Saravia F(2010)Short-term environmental enrichment enhances adult neurogenesis,vascular network and dendritic complexity in the hippocampus of type 1 diabetic mice.PLo S One 5:e13993.
Benka Wallén M,Franzén E,Nero H,Hagstr?mer M(2015)Levels and patterns of physical activity and sedentary behavior in elderly people with mild to moderate Parkinson disease.Phys Ther 95:1135-1141.
Bergman H,Deuschl G(2002)Pathophysiology of Parkinson’s disease:from clinical neurology to basic neuroscience and back.Mov Disord17 Suppl 3:S28-40.
Bhagya VR,Srikumar BN,Veena J,Shankaranarayana Rao BS(2017)Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity,anxiety,and memory deficits.J Neurosci Res 95:1602-1610.
Campêlo CLC,Santos JR,Silva AF,Dierschnabel AL,Pontes A,Cavalcante JS,Ribeiro AM,Silva RH(2017)Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice.Behav Brain Res 328:138-148.
Chabot A,Meus MA,Hertig V,Duquette N,Calderone A(2013)The neurogenic response of cardiac resident nestin(+)cells was associated with GAP43 upregulation and abrogated in a setting of type Idiabetes.Cardiovasc Diabetol 12:114.
Chang WH,Park CH,Kim DY,Shin YI,Ko MH,Lee A,Jang SY,Kim YH(2016)Cerebrolysin combined with rehabilitation promotes motor recovery in patients with severe motor impairment after stroke.BMC Neurol 16:31.
Collier TJ,Lipton J,Daley BF,Palfi S,Chu Y,Sortwell C,Bakay RA,Sladek JR Jr,Kordower JH(2007)Aging-related changes in the nigrostriatal dopamine system and the response to MPTP in nonhuman primates:diminished compensatory mechanisms as a prelude to parkinsonism.Neurobiol Dis 26:56-65.
Elbaz A,Carcaillon L,Kab S,Moisan F(2016)Epidemiology of Parkinson’s disease.Rev Neurol(Paris)172:14-26.
Flood JF,Morley JE(1998)Learning and memory in the SAMP8mouse.Neurosci Biobehav Rev 22:1-20.
Galvan A,Wichmann T(2008)Pathophysiology of parkinsonism.Clin Neurophysiol 119:1459-1474.
Garthe A,Roeder I,Kempermann G(2016)Mice in an enriched environment learn more flexibly because of adult hippocampal neurogenesis.Hippocampus 26:261-271.
Gorup D,Bohacek I,Milicevic T,Pochet R,Mitrecic D,Kriz J,Gajovic S(2015)Increased expression and colocalization of GAP43 and CASP3after brain ischemic lesion in mouse.Neurosci Lett 597:176-182.
Gu YL,Zhang LW,Ma N,Ye LL,Wang de X,Gao X(2014)Cognitive improvement of mice induced by exercise prior to traumatic brain injury is associated with cytochrome c oxidase.Neurosci Lett 570:86-91.
Hindle JV,Hurt CS,Burn DJ,Brown RG,Samuel M,Wilson KC,Clare L(2016)The effects of cognitive reserve and lifestyle on cognition and dementia in Parkinson’s disease--a longitudinal cohort study.Int J Geriatr Psychiatry 31:13-23.
Hosseiny S,Pietri M,Petit-Paitel A,Zarif H,Heurteaux C,Chabry J,Guyon A(2015)Differential neuronal plasticity in mouse hippocampus associated with various periods of enriched environment during postnatal development.Brain Struct Funct 220:3435-3448.
Huang J,Wu FF,He X,Li JP,Yan XX,Pan AH,Li ZY(2016)Effects of enriched environment on immature neurons in piriform cortex of a rat model of vascular dementia.Zhongguo Zuzhi Gongcheng Yanjiu20:4006-4012.
Jacobson RD,Virag I,Skene JH(1986)A protein associated with axon growth,GAP-43,is widely distributed and developmentally regulated in rat CNS.J Neurosci 6:1843-1855.
Jungling A,Reglodi D,Karadi ZN,Horvath G,Farkas J,Gaszner B,Tamas A(2017)Effects of postnatal enriched environment in a model of Parkinson’s disease in adult rats.Int J Mol Sci 18:E406.
Kakkar AK,Dahiya N(2015)Management of Parkinsons disease:Current and future pharmacotherapy.Eur J Pharmacol 750:74-81.
Kawamata T,Akiguchi I,Yagi H,Irino M,Sugiyama H,Akiyama H,Shimada A,Takemura M,Ueno M,Kitabayashi T,Ohnishi K,Seriu N,Higuchi K,Hosokawa M,Takeda T(1997)Neuropathological studies on strains of senescence-accelerated mice(SAM)with age-related deficits in learning and memory.Exp Gerontol 32:161-169.
Kazlauckas V,Pagnussat N,Mioranzza S,Kalinine E,Nunes F,Pettenuzzo L,Souza DO,Portela LV,Porciúncula LO,Lara DR(2011)Enriched environment effects on behavior,memory and BDNF in low and high exploratory mice.Physiol Behav 102:475-480.
Kotloski RJ,Sutula TP(2015)Environmental enrichment:evidence for an unexpected therapeutic influence.Exp Neurol 264:121-126.
Lach G,Bicca MA,Hoeller AA,Santos EC,Costa AP,de Lima TC(2016)Short-term enriched environment exposure facilitates fear extinction in adult rats:The NPY-Y1 receptor modulation.Neuropeptides 55:73-78.
La Hue SC,Comella CL,Tanner CM(2016)The best medicine?The influence of physical activity and inactivity on Parkinson’s disease.Mov Disord 31:1444-1454.
Lamotte G,Rafferty MR,Prodoehl J,Kohrt WM,Comella CL,Simuni T,Corcos DM(2015)Effects of endurance exercise training on the motor and non-motor features of Parkinson’s disease:a review.JParkinsons Dis 5:21-41.
Laviola G,Hannan AJ,Macri S,Solinas M,Jaber M(2008)Effects of enriched environment on animal models of neurodegenerative diseases and psychiatric disorders.Neurobiol Dis 31:159-168.
Liu J,Wang YY,Liu L,Wang QD,Yuan ZY,Zhang ZX,Gu P,Wang MW(2008)Damage to the nigrostriatal system in the MPTP-treated SAMP8 mouse.Neurosci Lett 448:184-188.
Liu J,Wang MW,Gu P,Ma QY,Wang YY,Geng Y,Yuan ZY,Cui DS,Zhang ZX,Ma L,Zhang BH,Zhou MG,Zhu AP(2010)Microglial activation and age-related dopaminergic neurodegeneration in MPTP-treated SAMP8 mice.Brain Res 1345:213-220.
Mahati K,Bhagya V,Christofer T,Sneha A,Shankaranarayana Rao BS(2016)Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity.Neurobiol Learn Mem 134 Pt B:379-391.
Mo C,Hannan AJ,Renoir T(2015)Environmental factors as modulators of neurodegeneration:insights from gene-environment interactions in Huntington’s disease.Neurosci Biobehav Rev 52:178-192.
O’Connor AM,Burton TJ,Leamey CA,Sawatari A(2014)The use of the puzzle box as a means of assessing the efficacy of environmental enrichment.J Vis Exp:e52225.
Obiang P,Maubert E,Bardou I,Nicole O,Launay S,Bezin L,Vivien D,Agin V(2011)Enriched housing reverses age-associated impairment of cognitive functions and t PA-dependent maturation of BDNF.Neurobiol Learn Mem 96:121-129.
Ohashi S,Mori A,Kurihara N,Mitsumoto Y,Nakai M(2006)Age-related severity of dopaminergic neurodegeneration to MPTP neurotoxicity causes motor dysfunction in C57BL/6 mice.Neurosci Lett 401:183-187.
Placha K,Luptakova D,Baciak L,Ujhazy E,Juranek I(2016)Neonatal brain injury as a consequence of insufficient cerebral oxygenation.Neuro Endocrinol Lett 37:79-96.
Pringsheim T,Jette N,Frolkis A,Steeves TD(2014)The prevalence of Parkinson’s disease:a systematic review and meta-analysis.Mov Disord 29:1583-1590.
Rainaldi MA,Perlman JM(2016)Pathophysiology of birth asphyxia.Clin Perinatol 43:409-422.
Reglódi D,Tamás A,Lengvári I,Toth G,Szalontay L,Lubics A(2006)Comparative study of the effects of PACAP in young,aging,and castrated males in a rat model of Parkinson’s disease.Ann N Y Acad Sci 1070:518-524.
Reglódi D,Renaud J,Tamas A,Tizabi Y,Socias SB,Del-Bel E,Raisman-Vozari R(2017)Novel tactics for neuroprotection in Parkinson’s disease:Role of antibiotics,polyphenols and neuropeptides.Prog Neurobiol 155:120-148.
Requejo C,Ruiz-Ortega JA,Cepeda H,Sharma A,Sharma HS,Ozkizilcik A,Tian R,Moessler H,Ugedo L,Lafuente JV(2018)Nanodelivery of cerebrolysin and rearing in enriched environment induce neuroprotective effects in a preclinical rat model of Parkinson’s disease.Mol Neurobiol 55:286-299.
Rosskothen-Kuhl N,Illing RB(2014)Gap43 transcription modulation in the adult brain depends on sensory activity and synaptic cooperation.PLo S One 9:e92624.
Schreiber S,Lin R,Haim L,Baratz-Goldstien R,Rubovitch V,Vaisman N,Pick CG(2014)Enriched environment improves the cognitive effects from traumatic brain injury in mice.Behav Brain Res 271:59-64.
Shih IF,Liew Z,Krause N,Ritz B(2016)Lifetime occupational and leisure time physical activity and risk of Parkinson’s disease.Parkinsonism Relat Disord 28:112-117.
Song JX,Sze SC,Ng TB,Lee CK,Leung GP,Shaw PC,Tong Y,Zhang YB(2012)Anti-Parkinsonian drug discovery from herbal medicines:what have we got from neurotoxic models?J Ethnopharmacol 139:698-711.
Spielman LJ,Little JP,Klegeris A(2016)Physical activity and exercise attenuate neuroinflammation in neurological diseases.Brain Res Bull 125:19-29.
Takeda T,Hosokawa M,Higuchi K(1997)Senescence-accelerated mouse(SAM):a novel murine model of senescence.Exp Gerontol32:105-109.
Takuma K,Maeda Y,Ago Y,Ishihama T,Takemoto K,Nakagawa A,Shintani N,Hashimoto H,Baba A,Matsuda T(2014)An enriched environment ameliorates memory impairments in PACAP-deficient mice.Behav Brain Res 272:269-278.
Tomas D,Prijanto AH,Burrows EL,Hannan AJ,Horne MK,Aumann TD(2015)Environmental modulations of the number of midbrain dopamine neurons in adult mice.J Vis Exp:52329.
Tsai SW,Tung YT,Chen HL,Shen CJ,Chuang CH,Tang TY,Chen CM(2013)Treadmill running upregulates the expression of acetylcholine receptor in rat gastrocnemius following botulinum toxin Ainjection.J Orthop Res 31:125-131.
van Praag H,Kempermann G,Gage FH(2000)Neural consequences of environmental enrichment.Nat Rev Neurosci 1:191-198.
Wang X,Chen A,Wu H,Ye M,Cheng H,Jiang X,Wang X,Zhang X,Wu D,Gu X,Shen F,Shan C,Yu D(2016)Enriched environment improves post-stroke cognitive impairment in mice by potential regulation of acetylation homeostasis in cholinergic circuits.Brain Res 1650:232-242.
White JH,Bartley E,Janssen H,Jordan LA,Spratt N(2015)Exploring stroke survivor experience of participation in an enriched environment:a qualitative study.Disabil Rehabil 37:593-600.
Wirdefeldt K,Adami HO,Cole P,Trichopoulos D,Mandel J(2011)Epidemiology and etiology of Parkinson’s disease:a review of the evidence.Eur J Epidemiol 26 Suppl 1:S1-58.
Wood LD,Neumiller JJ,Setter SM,Dobbins EK(2010)Clinical review of treatment options for select nonmotor symptoms of Parkinson’s disease.Am J Geriatr Pharmacother 8:294-315.
Young D,Lawlor PA,Leone P,Dragunow M,During MJ(1999)Environmental enrichment inhibits spontaneous apoptosis,prevents seizures and is neuroprotective.Nat Med 5:448-453.
Yuan Z,Wang M,Yan B,Gu P,Jiang X,Yang X,Cui D(2012)An enriched environment improves cognitive performance in mice from the senescence-accelerated prone mouse 8 strain:Role of upregulated neurotrophic factor expression in the hippocampus.Neural Regen Res 7:1797-1804.
Yuan ZY,Gu P,Liu L(2008)Effects of MPTP on spatial learning and memory ability and dopaminergic neurons in Nigra of senescence accelerated prone8 mice.Dier Junyi Daxue Xuebao 11:1337-1340.
Yuan ZY,Jiang XM,Gu P,Wang YX,Wang MW(2013)Effects of different feeding environments on learning and memory ability and hippocampal synapsin I in senescence accelerated-prone mice.Zhongguo Laonian Xue Zazhi 33:4196-4199.
Yuan ZY,Gu P,Liu L,Cui DS,Liu J,Wang YY(2009a)Effect of enriched environment on emotional behaviour in senescence accelerated-prone mice 8.Disi Junyi Daxue Xuebao 30:2231-2234.
Yuan ZY,Gu P,Liu L,Wang YY,Liu J,Cui DS,Geng Y,Zhang ZX,Zhu AP,Ma L,Wang MW(2009b)Neuroprotective effects of enriched environment in MPTP-treated SAMP8 mice.Neurosci Lett 454:6-10.
Baumgartel K,Mansuy IM(2012)Neural functions of calcineurin in synaptic plasticity and memory.Learn Mem 19:375-384.
Beauquis J,Roig P,De Nicola AF,Saravia F(2010)Short-term environmental enrichment enhances adult neurogenesis,vascular network and dendritic complexity in the hippocampus of type 1 diabetic mice.PLo S One 5:e13993.
Benka Wallén M,Franzén E,Nero H,Hagstr?mer M(2015)Levels and patterns of physical activity and sedentary behavior in elderly people with mild to moderate Parkinson disease.Phys Ther 95:1135-1141.
Bergman H,Deuschl G(2002)Pathophysiology of Parkinson’s disease:from clinical neurology to basic neuroscience and back.Mov Disord17 Suppl 3:S28-40.
Bhagya VR,Srikumar BN,Veena J,Shankaranarayana Rao BS(2017)Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity,anxiety,and memory deficits.J Neurosci Res 95:1602-1610.
Campêlo CLC,Santos JR,Silva AF,Dierschnabel AL,Pontes A,Cavalcante JS,Ribeiro AM,Silva RH(2017)Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice.Behav Brain Res 328:138-148.
Chabot A,Meus MA,Hertig V,Duquette N,Calderone A(2013)The neurogenic response of cardiac resident nestin(+)cells was associated with GAP43 upregulation and abrogated in a setting of type Idiabetes.Cardiovasc Diabetol 12:114.
Chang WH,Park CH,Kim DY,Shin YI,Ko MH,Lee A,Jang SY,Kim YH(2016)Cerebrolysin combined with rehabilitation promotes motor recovery in patients with severe motor impairment after stroke.BMC Neurol 16:31.
Collier TJ,Lipton J,Daley BF,Palfi S,Chu Y,Sortwell C,Bakay RA,Sladek JR Jr,Kordower JH(2007)Aging-related changes in the nigrostriatal dopamine system and the response to MPTP in nonhuman primates:diminished compensatory mechanisms as a prelude to parkinsonism.Neurobiol Dis 26:56-65.
Elbaz A,Carcaillon L,Kab S,Moisan F(2016)Epidemiology of Parkinson’s disease.Rev Neurol(Paris)172:14-26.
Flood JF,Morley JE(1998)Learning and memory in the SAMP8mouse.Neurosci Biobehav Rev 22:1-20.
Galvan A,Wichmann T(2008)Pathophysiology of parkinsonism.Clin Neurophysiol 119:1459-1474.
Garthe A,Roeder I,Kempermann G(2016)Mice in an enriched environment learn more flexibly because of adult hippocampal neurogenesis.Hippocampus 26:261-271.
Gorup D,Bohacek I,Milicevic T,Pochet R,Mitrecic D,Kriz J,Gajovic S(2015)Increased expression and colocalization of GAP43 and CASP3after brain ischemic lesion in mouse.Neurosci Lett 597:176-182.
Gu YL,Zhang LW,Ma N,Ye LL,Wang de X,Gao X(2014)Cognitive improvement of mice induced by exercise prior to traumatic brain injury is associated with cytochrome c oxidase.Neurosci Lett 570:86-91.
Hindle JV,Hurt CS,Burn DJ,Brown RG,Samuel M,Wilson KC,Clare L(2016)The effects of cognitive reserve and lifestyle on cognition and dementia in Parkinson’s disease--a longitudinal cohort study.Int J Geriatr Psychiatry 31:13-23.
Hosseiny S,Pietri M,Petit-Paitel A,Zarif H,Heurteaux C,Chabry J,Guyon A(2015)Differential neuronal plasticity in mouse hippocampus associated with various periods of enriched environment during postnatal development.Brain Struct Funct 220:3435-3448.
Huang J,Wu FF,He X,Li JP,Yan XX,Pan AH,Li ZY(2016)Effects of enriched environment on immature neurons in piriform cortex of a rat model of vascular dementia.Zhongguo Zuzhi Gongcheng Yanjiu20:4006-4012.
Jacobson RD,Virag I,Skene JH(1986)A protein associated with axon growth,GAP-43,is widely distributed and developmentally regulated in rat CNS.J Neurosci 6:1843-1855.
Jungling A,Reglodi D,Karadi ZN,Horvath G,Farkas J,Gaszner B,Tamas A(2017)Effects of postnatal enriched environment in a model of Parkinson’s disease in adult rats.Int J Mol Sci 18:E406.
Kakkar AK,Dahiya N(2015)Management of Parkinsons disease:Current and future pharmacotherapy.Eur J Pharmacol 750:74-81.
Kawamata T,Akiguchi I,Yagi H,Irino M,Sugiyama H,Akiyama H,Shimada A,Takemura M,Ueno M,Kitabayashi T,Ohnishi K,Seriu N,Higuchi K,Hosokawa M,Takeda T(1997)Neuropathological studies on strains of senescence-accelerated mice(SAM)with age-related deficits in learning and memory.Exp Gerontol 32:161-169.
Kazlauckas V,Pagnussat N,Mioranzza S,Kalinine E,Nunes F,Pettenuzzo L,Souza DO,Portela LV,Porciúncula LO,Lara DR(2011)Enriched environment effects on behavior,memory and BDNF in low and high exploratory mice.Physiol Behav 102:475-480.
Kotloski RJ,Sutula TP(2015)Environmental enrichment:evidence for an unexpected therapeutic influence.Exp Neurol 264:121-126.
Lach G,Bicca MA,Hoeller AA,Santos EC,Costa AP,de Lima TC(2016)Short-term enriched environment exposure facilitates fear extinction in adult rats:The NPY-Y1 receptor modulation.Neuropeptides 55:73-78.
La Hue SC,Comella CL,Tanner CM(2016)The best medicine?The influence of physical activity and inactivity on Parkinson’s disease.Mov Disord 31:1444-1454.
Lamotte G,Rafferty MR,Prodoehl J,Kohrt WM,Comella CL,Simuni T,Corcos DM(2015)Effects of endurance exercise training on the motor and non-motor features of Parkinson’s disease:a review.JParkinsons Dis 5:21-41.
Laviola G,Hannan AJ,Macri S,Solinas M,Jaber M(2008)Effects of enriched environment on animal models of neurodegenerative diseases and psychiatric disorders.Neurobiol Dis 31:159-168.
Liu J,Wang YY,Liu L,Wang QD,Yuan ZY,Zhang ZX,Gu P,Wang MW(2008)Damage to the nigrostriatal system in the MPTP-treated SAMP8 mouse.Neurosci Lett 448:184-188.
Liu J,Wang MW,Gu P,Ma QY,Wang YY,Geng Y,Yuan ZY,Cui DS,Zhang ZX,Ma L,Zhang BH,Zhou MG,Zhu AP(2010)Microglial activation and age-related dopaminergic neurodegeneration in MPTP-treated SAMP8 mice.Brain Res 1345:213-220.
Mahati K,Bhagya V,Christofer T,Sneha A,Shankaranarayana Rao BS(2016)Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity.Neurobiol Learn Mem 134 Pt B:379-391.
Mo C,Hannan AJ,Renoir T(2015)Environmental factors as modulators of neurodegeneration:insights from gene-environment interactions in Huntington’s disease.Neurosci Biobehav Rev 52:178-192.
O’Connor AM,Burton TJ,Leamey CA,Sawatari A(2014)The use of the puzzle box as a means of assessing the efficacy of environmental enrichment.J Vis Exp:e52225.
Obiang P,Maubert E,Bardou I,Nicole O,Launay S,Bezin L,Vivien D,Agin V(2011)Enriched housing reverses age-associated impairment of cognitive functions and t PA-dependent maturation of BDNF.Neurobiol Learn Mem 96:121-129.
Ohashi S,Mori A,Kurihara N,Mitsumoto Y,Nakai M(2006)Age-related severity of dopaminergic neurodegeneration to MPTP neurotoxicity causes motor dysfunction in C57BL/6 mice.Neurosci Lett 401:183-187.
Placha K,Luptakova D,Baciak L,Ujhazy E,Juranek I(2016)Neonatal brain injury as a consequence of insufficient cerebral oxygenation.Neuro Endocrinol Lett 37:79-96.
Pringsheim T,Jette N,Frolkis A,Steeves TD(2014)The prevalence of Parkinson’s disease:a systematic review and meta-analysis.Mov Disord 29:1583-1590.
Rainaldi MA,Perlman JM(2016)Pathophysiology of birth asphyxia.Clin Perinatol 43:409-422.
Reglódi D,Tamás A,Lengvári I,Toth G,Szalontay L,Lubics A(2006)Comparative study of the effects of PACAP in young,aging,and castrated males in a rat model of Parkinson’s disease.Ann N Y Acad Sci 1070:518-524.
Reglódi D,Renaud J,Tamas A,Tizabi Y,Socias SB,Del-Bel E,Raisman-Vozari R(2017)Novel tactics for neuroprotection in Parkinson’s disease:Role of antibiotics,polyphenols and neuropeptides.Prog Neurobiol 155:120-148.
Requejo C,Ruiz-Ortega JA,Cepeda H,Sharma A,Sharma HS,Ozkizilcik A,Tian R,Moessler H,Ugedo L,Lafuente JV(2018)Nanodelivery of cerebrolysin and rearing in enriched environment induce neuroprotective effects in a preclinical rat model of Parkinson’s disease.Mol Neurobiol 55:286-299.
Rosskothen-Kuhl N,Illing RB(2014)Gap43 transcription modulation in the adult brain depends on sensory activity and synaptic cooperation.PLo S One 9:e92624.
Schreiber S,Lin R,Haim L,Baratz-Goldstien R,Rubovitch V,Vaisman N,Pick CG(2014)Enriched environment improves the cognitive effects from traumatic brain injury in mice.Behav Brain Res 271:59-64.
Shih IF,Liew Z,Krause N,Ritz B(2016)Lifetime occupational and leisure time physical activity and risk of Parkinson’s disease.Parkinsonism Relat Disord 28:112-117.
Song JX,Sze SC,Ng TB,Lee CK,Leung GP,Shaw PC,Tong Y,Zhang YB(2012)Anti-Parkinsonian drug discovery from herbal medicines:what have we got from neurotoxic models?J Ethnopharmacol 139:698-711.
Spielman LJ,Little JP,Klegeris A(2016)Physical activity and exercise attenuate neuroinflammation in neurological diseases.Brain Res Bull 125:19-29.
Takeda T,Hosokawa M,Higuchi K(1997)Senescence-accelerated mouse(SAM):a novel murine model of senescence.Exp Gerontol32:105-109.
Takuma K,Maeda Y,Ago Y,Ishihama T,Takemoto K,Nakagawa A,Shintani N,Hashimoto H,Baba A,Matsuda T(2014)An enriched environment ameliorates memory impairments in PACAP-deficient mice.Behav Brain Res 272:269-278.
Tomas D,Prijanto AH,Burrows EL,Hannan AJ,Horne MK,Aumann TD(2015)Environmental modulations of the number of midbrain dopamine neurons in adult mice.J Vis Exp:52329.
Tsai SW,Tung YT,Chen HL,Shen CJ,Chuang CH,Tang TY,Chen CM(2013)Treadmill running upregulates the expression of acetylcholine receptor in rat gastrocnemius following botulinum toxin Ainjection.J Orthop Res 31:125-131.
van Praag H,Kempermann G,Gage FH(2000)Neural consequences of environmental enrichment.Nat Rev Neurosci 1:191-198.
Wang X,Chen A,Wu H,Ye M,Cheng H,Jiang X,Wang X,Zhang X,Wu D,Gu X,Shen F,Shan C,Yu D(2016)Enriched environment improves post-stroke cognitive impairment in mice by potential regulation of acetylation homeostasis in cholinergic circuits.Brain Res 1650:232-242.
White JH,Bartley E,Janssen H,Jordan LA,Spratt N(2015)Exploring stroke survivor experience of participation in an enriched environment:a qualitative study.Disabil Rehabil 37:593-600.
Wirdefeldt K,Adami HO,Cole P,Trichopoulos D,Mandel J(2011)Epidemiology and etiology of Parkinson’s disease:a review of the evidence.Eur J Epidemiol 26 Suppl 1:S1-58.
Wood LD,Neumiller JJ,Setter SM,Dobbins EK(2010)Clinical review of treatment options for select nonmotor symptoms of Parkinson’s disease.Am J Geriatr Pharmacother 8:294-315.
Young D,Lawlor PA,Leone P,Dragunow M,During MJ(1999)Environmental enrichment inhibits spontaneous apoptosis,prevents seizures and is neuroprotective.Nat Med 5:448-453.
Yuan Z,Wang M,Yan B,Gu P,Jiang X,Yang X,Cui D(2012)An enriched environment improves cognitive performance in mice from the senescence-accelerated prone mouse 8 strain:Role of upregulated neurotrophic factor expression in the hippocampus.Neural Regen Res 7:1797-1804.
Yuan ZY,Gu P,Liu L(2008)Effects of MPTP on spatial learning and memory ability and dopaminergic neurons in Nigra of senescence accelerated prone8 mice.Dier Junyi Daxue Xuebao 11:1337-1340.
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