Assessment of Developmental Milestones in Rodents

Heyser, Charles J.

doi:10.1002/0471142301.ns0818s25

Cited by 120 publications

(134 citation statements)

References 42 publications

(57 reference statements)

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“…WT and Bdnf-e1, -e2, -e4, and -e6 animals were tested for developmental weight, eye opening, and selected reflexes from P3 to P14 as described (Heyser, 2004). Briefly, surface righting reflex was analyzed by placing a pup on its back and recording the latency to turn over onto its belly.…”

Section: Assessment Of Developmental Milestonesmentioning

confidence: 99%

Functional Role of BDNF Production from Unique Promoters in Aggression and Serotonin Signaling

Maynard

Hill

Calcaterra

et al. 2015

Neuropsychopharmacol

102

150

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Brain-derived neurotrophic factor (BDNF) regulates diverse biological functions ranging from neuronal survival and differentiation during development to synaptic plasticity and cognitive behavior in the adult. BDNF disruption in both rodents and humans is associated with neurobehavioral alterations and psychiatric disorders. A unique feature of Bdnf transcription is regulation by nine individual promoters, which drive expression of variants that encode an identical protein. It is hypothesized that this unique genomic structure may provide flexibility that allows different factors to regulate BDNF signaling in distinct cell types and circuits. This has led to the suggestion that isoforms may regulate specific BDNF-dependent functions; however, little scientific support for this idea exists. We generated four novel mutant mouse lines in which BDNF production from one of the four major promoters (I, II, IV, or VI) is selectively disrupted (Bdnf-e1, -e2, -e4, and -e6 mice) and used a comprehensive comparator approach to determine whether different Bdnf transcripts are associated with specific BDNF-dependent molecular, cellular, and behavioral phenotypes. Bdnf-e1 and -e2 mutant males displayed heightened aggression accompanied by convergent expression changes in specific genes associated with serotonin signaling. In contrast, BDNF-e4 and -e6 mutants were not aggressive but displayed impairments associated with GABAergic gene expression. Moreover, quantifications of BDNF protein in the hypothalamus, prefrontal cortex, and hippocampus revealed that individual Bdnf transcripts make differential, regionspecific contributions to total BDNF levels. The results highlight the biological significance of alternative Bdnf transcripts and provide evidence that individual isoforms serve distinct molecular and behavioral functions.

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Section: Assessment Of Developmental Milestonesmentioning

confidence: 99%

Functional Role of BDNF Production from Unique Promoters in Aggression and Serotonin Signaling

Maynard

Hill

Calcaterra

et al. 2015

Neuropsychopharmacol

102

150

View full text Add to dashboard Cite

show abstract

“…A detailed description of each behavior is available in Chapter 8, Current Protocols of Neuroscience (Heyser et al, 2001). Two cerebellar neuron reflexes were tested: (1) righting reflex.…”

Section: Postnatal Neurobehavioral Analysismentioning

confidence: 99%

The Knockout of Secretin in Cerebellar Purkinje Cells Impairs Mouse Motor Coordination and Motor Learning

Zhang

Chung

Chow

2013

Neuropsychopharmacol

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Secretin (SCT) was first considered to be a gut hormone regulating gastrointestinal functions when discovered. Recently, however, central actions of SCT have drawn intense research interest and are supported by the broad distribution of SCT in specific neuronal populations and by in vivo physiological studies regarding its role in water homeostasis and food intake. The direct action of SCT on a central neuron was first discovered in cerebellar Purkinje cells in which SCT from cerebellar Purkinje cells was found to potentiate GABAergic inhibitory transmission from presynaptic basket cells. Because Purkinje neurons have a major role in motor coordination and learning functions, we hypothesize a behavioral modulatory function for SCT. In this study, we successfully generated a mouse model in which the SCT gene was deleted specifically in Purkinje cells. This mouse line was tested together with SCT knockout and SCT receptor knockout mice in a full battery of behavioral tasks. We found that the knockout of SCT in Purkinje neurons did not affect general motor ability or the anxiety level in open field tests. However, knockout mice did exhibit impairments in neuromuscular strength, motor coordination, and motor learning abilities, as shown by wire hanging, vertical climbing, and rotarod tests. In addition, SCT knockout in Purkinje cells possibly led to the delayed development of motor neurons, as supported by the later occurrence of key neural reflexes. In summary, our data suggest a role in motor coordination and motor learning for SCT expressed in cerebellar Purkinje cells.

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“…A 16 x 18 fiberglass screen wire is used. The average age for a rodent to be able to grasp a horizontal screen is PND 8 with a range from PND 5 -15 15 . Fox used the four limb horizontal screen test from PND 2 -21 10 .…”

Section: Negative Geotaxismentioning

confidence: 99%

“…Repeat for a total of three trials and average the trials. NOTE: The grasping reflex usually appears in rodents at PND 7 with a range from PND 3 -15 15 . Each paw is tested individually, thus the test can reveal front-or hindlimb issues, as well as sidedness issues.…”

Section: Grip Strengthmentioning

confidence: 99%

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A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy

Feather-Schussler

Ferguson

2016

JoVE

124

162

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As the sheer number of transgenic mice strains grow and rodent models of pediatric disease increase, there is an expanding need for a comprehensive, standardized battery of neonatal mouse motor tests. These tests can validate injury or disease models, determine treatment efficacy and/or assess motor behaviors in new transgenic strains. This paper presents a series of neonatal motor tests to evaluate general motor function, including ambulation, hindlimb foot angle, surface righting, negative geotaxis, front-and hindlimb suspension, grasping reflex, four limb grip strength and cliff aversion. Mice between the ages of post-natal day 2 to 14 can be used. In addition, these tests can be used for a wide range of neurological and neuromuscular pathologies, including cerebral palsy, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, neurodegenerative diseases, and neuromuscular disorders. These tests can also be used to determine the effects of pharmacological agents, as well as other types of therapeutic interventions. In this paper, motor deficits were evaluated in a novel neonatal mouse model of cerebral palsy that combines hypoxia, ischemia and inflammation. Forty-eight hours after injury, five tests out of the nine showed significant motor deficits: ambulation, hindlimb angle, hindlimb suspension, four limb grip strength, and grasping reflex. These tests revealed weakness in the hindlimbs, as well as fine motor skills such as grasping, which are similar to the motor deficits seen in human cerebral palsy patients.

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Assessment of Developmental Milestones in Rodents

Cited by 120 publications

References 42 publications

Functional Role of BDNF Production from Unique Promoters in Aggression and Serotonin Signaling

Functional Role of BDNF Production from Unique Promoters in Aggression and Serotonin Signaling

The Knockout of Secretin in Cerebellar Purkinje Cells Impairs Mouse Motor Coordination and Motor Learning

A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy

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