Climbing fiber development: do neurotrophins have a part to play?

Sherrard, Rachel M.; Bower, Adrian J.

doi:10.1080/147342202320883579

Cited by 30 publications

(29 citation statements)

References 91 publications

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“…19 Thus, one speculative explanation is that the faster motor recovery from a cerebellar lesion in enriched rats may be associated with a greater increase in NGF.…”

Section: Discussionmentioning

confidence: 99%

“…Neurotrophins in the cerebellum have a role in neuronal regulation during brain development 19 and in neuroprotection [20][21][22] from glutamate-induced neurotoxicity. To date, no study has addressed the question on whether the prolonged exposure to complex environments is able to modify the recovery from deficits elicited by surgical or traumatic ablations of cerebellar regions.…”

Section: Introductionmentioning

confidence: 99%

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Enriched Environment Improves Motor Function and Increases Neurotrophins in Hemicerebellar Lesioned Rats

Gelfo

Cutuli

Foti

et al. 2010

Neurorehabil Neural Repair

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Background. Environmental enrichment (EE) defined as "a combination of complex inanimate and social stimulation" influences brain function and anatomy by enhancing sensory, cognitive, motor, and social stimulation. The beneficial effects of EE in the presence of brain damage have been partially attributed to upregulation of neurotrophins, proteins involved in neuronal survival and in activity-dependent plasticity. Objective. The authors tested the hypothesis that EE may have advantageous effects on recovery of motor function after cerebellar damage, associated with changes in local neurotrophin production. Methods. They performed a hemicerebellectomy in rats previously exposed to EE or reared in standard conditions. The time course of compensation of motor symptoms was analyzed in both lesioned groups. Then, the local production of the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the spared hemicerebellum and other extracerebellar regions was evaluated. Results. Long-term exposure to EE accelerated the motor recovery in hemicerebellectomized rats and elicited an increase in NGF levels in the spared hemicerebellum, as compared with nonenriched lesioned and control rats. BDNF levels were higher in hemicerebellectomized rats but not influenced by EE. In the frontal cortex, both NGF and BDNF levels were upregulated in hemicerebellectomized enriched rats as compared with hemicerebellectomized nonenriched and control rats. Conclusions. This study suggests that the beneficial effects of EE on motor symptoms after cerebellar damage may be, at least partly, because of modulation of neurotrophic proteins involved in the regeneration processes.

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“…19 Thus, one speculative explanation is that the faster motor recovery from a cerebellar lesion in enriched rats may be associated with a greater increase in NGF.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enriched Environment Improves Motor Function and Increases Neurotrophins in Hemicerebellar Lesioned Rats

Gelfo

Cutuli

Foti

et al. 2010

Neurorehabil Neural Repair

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“…In addition to BDNF in cerebellar granule cells, BDNF in the inferior olive (Conner et al, 1997;Li et al, 2001) is thought to act on postsynaptic Purkinje cells via presynaptic CF terminals originating from the inferior olive (Sherrard and Bower, 2002). CAPS1, but not CAPS2, is expressed in the inferior olive (Sadakata et al, 2006) and was colocalized with VGLUT2 (supplemental Fig.…”

Section: The Secretion Defect In Caps2mentioning

confidence: 99%

Impaired Cerebellar Development and Function in Mice Lacking CAPS2, a Protein Involved in Neurotrophin Release

Sadakata¹,

Kakegawa²,

Mizoguchi³

et al. 2007

J. Neurosci.

144

138

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Ca2ϩ -dependent activator protein for secretion 2 (CAPS2/CADPS2) is a secretory granule-associated protein that is abundant at the parallel fiber terminals of granule cells in the mouse cerebellum and is involved in the release of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF), both of which are required for cerebellar development. The human homolog gene on chromosome 7 is located within susceptibility locus 1 of autism, a disease characterized by several cerebellar morphological abnormalities. Here we report that CAPS2 knock-out mice are deficient in the release of NT-3 and BDNF, and they consequently exhibit suppressed phosphorylation of Trk receptors in the cerebellum; these mice exhibit pronounced impairments in cerebellar development and functions, including neuronal survival, differentiation and migration of postmitotic granule cells, dendritogenesis of Purkinje cells, lobulation between lobules VI and VII, structure and vesicular distribution of parallel fiber-Purkinje cell synapses, paired-pulse facilitation at parallel fiber-Purkinje cell synapses, rotarod motor coordination, and eye movement plasticity in optokinetic training. Increased granule cell death of the external granular layer was noted in lobules VI-VII and IX, in which high BDNF and NT-3 levels are specifically localized during cerebellar development. Therefore, the deficiency of CAPS2 indicates that CAPS2-mediated neurotrophin release is indispensable for normal cerebellar development and functions, including neuronal differentiation and survival, morphogenesis, synaptic function, and motor leaning/control. The possible involvement of the CAPS2 gene in the cerebellar deficits of autistic patients is discussed.

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“…Finally, changes in mRNA levels are not always directly reflected in protein levels. NT-3 and NT-4 play an important role in the development of the climbing fibre system of the cerebellar Purkinje cells (PCs), and moreover, NT-3 selectively increases cultured PCs survival [48][49][50][51]. These cells are the primary efferent neurons of the cerebellar cortex, and its potential involvement in ASD has long been proposed [52].…”

Section: Discussionmentioning

confidence: 99%

Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder

et al. 2014

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Autism spectrum disorders (ASD) comprise neurodevelopmental disorders with clinical onset during the first years of life. The identification of peripheral biomarkers could significantly impact diagnosis and an individualized, early treatment. Although the aetiology of ASD remains poorly understood, there is increasing evidence that neurotrophins and their receptors represent a group of candidate genes for ASD pathophysiology and biomarker research. Total messenger RNA (mRNA) from whole blood was obtained from adolescents and adults diagnosed as ASD (n = 21) according to DSM-IV criteria and confirmed by the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) algorithms, as well as healthy controls (n = 10). The mRNA expression of neurotrophins (BDNF, NT3 and NT4) and their receptors (TrkA, TrkB and p75 (NTR) ) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, social cognition abilities of ASD patients and controls were determined according to three Theory of Mind (ToM) tests (Reading the Mind in the Eyes, Faux pas, and Happé stories). The NT3 and NT4 mRNA expression in the whole blood was significantly lower in ASD compared to healthy controls, while p75(NTR) was higher (P < 0.005). In addition, lower scores in three of the ToM tests were observed in ASD subjects compared to controls. A significant (P < 0.005) ToM impairment in Happé stories test was demonstrated in ASD. Nevertheless, no correlations were observed between neurotrophins and their receptors expressions and measures of ToM. Given their potential as peripheral blood-based biomarkers, NT3, NT4 and p75 (NTR) mRNA expression patterns may be useful tools for a more personalized diagnostics and therapy in ASD. Further investigations with larger numbers of samples are needed to verify these results.

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Climbing fiber development: do neurotrophins have a part to play?

Cited by 30 publications

References 91 publications

Enriched Environment Improves Motor Function and Increases Neurotrophins in Hemicerebellar Lesioned Rats

Enriched Environment Improves Motor Function and Increases Neurotrophins in Hemicerebellar Lesioned Rats

Impaired Cerebellar Development and Function in Mice Lacking CAPS2, a Protein Involved in Neurotrophin Release

Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder

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