SHIRPA as a Neurological Screening Battery in Mice

Lalonde, Robert; Filali, Mohammed; Strazielle, C.

doi:10.1002/cpz1.135

Cited by 11 publications

(7 citation statements)

References 121 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Autophagy has previously been shown to promote memory formation (Glatigny et al , 2019). To further characterize the effects of neuronal ATG5 deletion on mouse behavior, we employed the SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA)‐based test battery, which includes 22 measures of motor activity, postural control, emotional reactivity, and visual and auditory reflexes (Lalonde et al , 2021). We found that although mice lacking ATG5 in either excitatory or inhibitory neurons exhibited only minor neurological abnormalities (Appendix Fig S1H and I), both the Atg5 flox: CamKII α‐Cre and Atg5 flox :Slc32a1‐Cre KO lines responded with potentiated startle reflex to stimulus presentation compared to their control littermates (i.e.…”

Section: Resultsmentioning

confidence: 99%

Autophagy regulates neuronal excitability by controlling cAMP/protein kinase A signaling at the synapse

et al. 2022

View full text Add to dashboard Cite

Autophagy provides nutrients during starvation and eliminates detrimental cellular components. However, accumulating evidence indicates that autophagy is not merely a housekeeping process. Here, by combining mouse models of neuron-specific ATG5 deficiency in either excitatory or inhibitory neurons with quantitative proteomics, high-content microscopy, and live-imaging approaches, we show that autophagy protein ATG5 functions in neurons to regulate cAMP-dependent protein kinase A (PKA)-mediated phosphorylation of a synapse-confined proteome. This function of ATG5 is independent of bulk turnover of synaptic proteins and requires the targeting of PKA inhibitory R1 subunits to autophagosomes. Neuronal loss of ATG5 causes synaptic accumulation of PKA-R1, which sequesters the PKA catalytic subunit and diminishes cAMP/PKAdependent phosphorylation of postsynaptic cytoskeletal proteins that mediate AMPAR trafficking. Furthermore, ATG5 deletion in glutamatergic neurons augments AMPAR-dependent excitatory neurotransmission and causes the appearance of spontaneous recurrent seizures in mice. Our findings identify a novel role of autophagy in regulating PKA signaling at glutamatergic synapses and suggest the PKA as a target for restoration of synaptic function in neurodegenerative conditions with autophagy dysfunction.

show abstract

Section: Resultsmentioning

confidence: 99%

Autophagy regulates neuronal excitability by controlling cAMP/protein kinase A signaling at the synapse

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Gross phenotype assessment of motor and sensory function of aged mice was performed using elements of the primary screen of the SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA) test ( Rogers et al, 1997 ; Lalonde et al, 2021 ). This is a set of functional assessments that are designed to identify and systematically quantify abnormalities in murine muscle tone, lower motor neuron and spinocerebellar function, sensory and autonomic ability and motor coordination/capabilities.…”

Section: Methodsmentioning

confidence: 99%

C-type natriuretic peptide preserves central neurological function by maintaining blood-brain barrier integrity

Pérez‐Ternero

Pallier

Tremoleda

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

C-type natriuretic peptide (CNP) is highly expressed in the central nervous system (CNS) and key to neuronal development; however, a broader role for CNP in the CNS remains unclear. To address this deficit, we investigated behavioral, sensory and motor abnormalities and blood-brain barrier (BBB) integrity in a unique mouse model with inducible, global deletion of CNP (gbCNP–/–). gbCNP–/– mice and wild-type littermates at 12 (young adult) and 65 (aged) weeks of age were investigated for changes in gait and motor coordination (CatWalk™ and rotarod tests), anxiety-like behavior (open field and elevated zero maze tests), and motor and sensory function (modified neurological severity score [mNSS] and primary SHIRPA screen). Vascular permeability was assessed in vivo (Miles assay) with complementary in vitro studies conducted in primary murine brain endothelial cells. Young adult gbCNP–/– mice had normal gait but reduced motor coordination, increased locomotor activity in the open field and elevated zero maze, and had a higher mNSS score. Aged gbCNP–/– animals developed recurrent spontaneous seizures and had impaired gait and wide-ranging motor and sensory dysfunction. Young adult and aged gbCNP–/– mice exhibited increased BBB permeability, which was partially restored in vitro by CNP administration. Cultured brain endothelial cells from gbCNP–/– mice had an abnormal ZO-1 protein distribution. These data suggest that lack of CNP in the CNS impairs tight junction protein arrangement and increases BBB permeability, which is associated with changes in locomotor activity, motor coordination and late-onset seizures.

show abstract

“…Like human neurological exams, rodent observational batteries often serve as a first-tier test to identify “an effect.” Examples include the Functional Observational Battery ( US EPA, 1994b ; Moser and Kallman, 2018 ; Gauvin, 2021 ) and the SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA) ( Rogers et al, 2001 ; Lalonde et al, 2021 ). Additional batteries have been developed for assessing vestibular dysfunction ( Maroto et al, 2021 ), various genetic manipulations ( Brown et al, 2000 ), and neonatal function ( Fox, 1965 ; Brown et al, 2000 ; Feather-Schussler and Ferguson, 2016 ; Soria-Ortiz et al, 2021 ).…”

Section: Behavioral Assessmentsmentioning

confidence: 99%

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

Harry¹,

McBride²,

Witchey³

et al. 2022

Front. Toxicol.

View full text Add to dashboard Cite

With the appreciation that behavior represents the integration and complexity of the nervous system, neurobehavioral phenotyping and assessment has seen a renaissance over the last couple of decades, resulting in a robust database on rodent performance within various testing paradigms, possible associations with human disorders, and therapeutic interventions. The interchange of data across behavior and other test modalities and multiple model systems has advanced our understanding of fundamental biology and mechanisms associated with normal functions and alterations in the nervous system. While there is a demonstrated value and power of neurobehavioral assessments for examining alterations due to genetic manipulations, maternal factors, early development environment, the applied use of behavior to assess environmental neurotoxicity continues to come under question as to whether behavior represents a sensitive endpoint for assessment. Why is rodent behavior a sensitive tool to the neuroscientist and yet, not when used in pre-clinical or chemical neurotoxicity studies? Applying new paradigms and evidence on the biological basis of behavior to neurobehavioral testing requires expertise and refinement of how such experiments are conducted to minimize variability and maximize information. This review presents relevant issues of methods used to conduct such test, sources of variability, experimental design, data analysis, interpretation, and reporting. It presents beneficial and critical limitations as they translate to the in vivo environment and considers the need to integrate across disciplines for the best value. It proposes that a refinement of behavioral assessments and understanding of subtle pronounced differences will facilitate the integration of data obtained across multiple approaches and to address issues of translation.

show abstract

SHIRPA as a Neurological Screening Battery in Mice

Cited by 11 publications

References 121 publications

Autophagy regulates neuronal excitability by controlling cAMP/protein kinase A signaling at the synapse

Autophagy regulates neuronal excitability by controlling cAMP/protein kinase A signaling at the synapse

C-type natriuretic peptide preserves central neurological function by maintaining blood-brain barrier integrity

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

Contact Info

Product

Resources

About