Prenatal stress induces alterations in cerebellar nitric oxide that are correlated with deficits in spatial memory in rat’s offspring

Maur, Damián Gustavo; Romero, Carolina; Burdet, Berenice; Palumbo, María Laura; Zorrilla-Zubilete, María Aurelia

doi:10.1016/j.neuint.2012.09.006

Cited by 11 publications

(11 citation statements)

References 55 publications

(64 reference statements)

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“…Alterations of biochemical mechanisms underlying cerebellar synaptic plasticity might be involved in the effects reported here [49-51]. A GAD65Ab-mediated alteration of the NO pathway would trigger neurotoxic processes leading to altered behavioral outcome.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal antibodies to 65kDa glutamate decarboxylase induce epitope specific effects on motor and cognitive functions in rats

Hampe

Petrosini

Bartolo

et al. 2013

Orphanet J Rare Dis

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BackgroundStiff Person Syndrome (SPS) is a rare autoimmune movement disorder characterized by the presence of autoantibodies specific to the smaller isoform of glutamate decarboxylase (GAD65). A pathological role of these antibodies has been suggested by their capacity to inhibit GAD65 enzyme activity and by the observation that rats receiving cerebellar injections of GAD65Ab showed cerebellar motor hyperexcitability. To assess the effect of epitope-specific GAD65Ab on cognitive and motor functions, we conducted behavioral experiments in rats that received cerebellar injections with two distinct monoclonal GAD65Ab (b96.11 and b78).MethodsRats received three injections of GAD65Ab b96.11 (5 or 7 μg), GAD65Ab b78 (5 or 7 μg), or saline at the level of three cerebellar nuclei. Animals were submitted to neurological evaluation and Morris Water Maze (MWM) test. Cellular internalization of GAD65Ab was analyzed by Flow Cytometry, Fluorescence and Bright Field microscopy.ResultsMonoclonal GAD65Ab induced dose-dependent and epitope-specific effects on motor and cognitive functions. Injections of the higher dose altered motor and spatial procedural behaviors, while the lower dose induced only modest cerebellar motor symptoms and did not affect MWM performances. While b96.11 provoked immediate severe effects, which rapidly decreased, b78 induced moderate but prolonged effects. Both GAD65Ab were taken up by live cells in a dose-dependent manner.ConclusionsOur findings support the hypothesis that epitope-specific GAD65Ab induce cerebellar dysfunction impairing motor and procedural abilities. This is the first demonstration of a critical role of cerebellar nuclei GAD65 enzyme in procedural spatial functions.

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Section: Discussionmentioning

confidence: 99%

Monoclonal antibodies to 65kDa glutamate decarboxylase induce epitope specific effects on motor and cognitive functions in rats

Hampe

Petrosini

Bartolo

et al. 2013

Orphanet J Rare Dis

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“…Entre estos últimos, se ha verificado que el óxido nítrico juega un importante rol en los procesos de potenciación sináptica de larga duración hipocámpica y de depresión sináptica de larga duración cerebelar 1 ; particularmente en el sistema nervioso central, el neuromodulador estaría implicado en la modulación de los procesos de aprendizaje y memoria y en patologías del espectro afectivo. En este sentido, se han corroborado niveles aumentados de óxido nítrico sintasa en animales sometidos a EP, preconizándose que un aumento en la concentración de óxido nítrico sería conducente a mecanismos de neurotoxicidad a largo plazo 17 .…”

Section: Respuesta Neurotóxica Ante El Estrésunclassified

Efectos neurobiológicos del estrés prenatal sobre el nuevo ser

Cáceres

Martínez-Aguayo

Arancibia

et al. 2017

Rev. chil. neuro-psiquiatr.

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“…Furthermore, prenatal exposure to glucocorticoids leads to increased adult CRH levels in the central nucleus of the amygdala, a key region in the regulation of fear and anxiety (Cratty et al 1995). Exposure to PS has three major effects on adult behaviour: learning impairments, especially in aging rats (Valle et al 1999;Maur et al 2012); and increases in anxiety-and depression-related behaviours (Vallee et al 1997). …”

Section: Nitric Oxide In the Stress Axismentioning

confidence: 99%

Perinatal Programming of Neurodevelopment

Antonelli¹

2015

Advances in Neurobiology

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Volume 10Advances in Neurobiology covers basic research in neurobiology and neurochemistry. It provides in-depth, book-length treatment of some of the most important topics in neuroscience including molecular and pharmacological aspects. The main audiences of the series are basic science researchers and graduate students as well as clinicians including neuroscientists (neurobiologists and neurochemists) and neurologists.More information about this series at

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Prenatal stress induces alterations in cerebellar nitric oxide that are correlated with deficits in spatial memory in rat’s offspring

Cited by 11 publications

References 55 publications

Monoclonal antibodies to 65kDa glutamate decarboxylase induce epitope specific effects on motor and cognitive functions in rats

Monoclonal antibodies to 65kDa glutamate decarboxylase induce epitope specific effects on motor and cognitive functions in rats

Efectos neurobiológicos del estrés prenatal sobre el nuevo ser

Perinatal Programming of Neurodevelopment

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