Behavioral and neurobiological changes in C57BL/6 mouse exposed to cuprizone: effects of antipsychotics.

Recent human studies suggest a role for altered oligodendrocytes in the pathophysiology of schizophrenia. Our recent animal study has reported some schizophrenia-like behaviors in mice exposed to cuprizone (Xu et al., 2009), a copper chelator that has been shown to selectively damage the white matter.

Behavioral and neurobiological changes in C57BL/6 mice exposed to cuprizone.

C57BL/6 mice were given 0.2% cuprizone (CPZ) for 2 to 6 weeks while controls ate the same diet without CPZ. At various time points the animals were subjected to behavioral tests and their brains were analyzed.

Region-specific susceptibilities to cuprizone-induced lesions in the mouse forebrain: Implications for the pathophysiology of schizophrenia.

Cuprizone (CPZ) is a neurotoxic agent acting as a copper chelator. In our recent study, C57BL/6 mice given dietary CPZ (0.2%) showed impairments in spatial working memory, social interaction, and prepulse inhibition.

Localization of the serotonergic terminal fields modulating seizures in the genetically epilepsy-prone rat.

Serotonin (5-HT) has been shown to exert antiepileptic effects in a variety of generalized convulsive seizure models, particularly the genetically epilepsy-prone rat (GEPR). The present study was designed to identify the region/site(s) where 5-HT exerts anticonvulsant effects in the GEPR-9, a model in which sound-evoked generalized tonic-clonic seizures (GTCS) are highly sensitive to manipulations in 5-HT concentration. Because the 5-HT reuptake inhibitor, fluoxetine, was known to exert anticonvulsant effects in GEPR-9s via a 5-HT-dependent mechanism, we utilized selective regional 5-HT depletion in combination with systemic fluoxetine administration to find the site where a 5-HT deficit would prevent the anticonvulsant action of fluoxetine.

Vagus nerve stimulation may protect GABAergic neurons following traumatic brain injury in rats: An immunocytochemical study.

Seizures and subclinical seizures occur following experimental brain injury in rats and may result from inhibitory neuron loss. This study numerically compares cortical and hippocampal glutamic acid decarboxylase (GAD) positive neurons between sham fluid percussion injury (FPI), FPI with sham Vagus Nerve Simulation (VNS), and FPI with chronic intermittent VNS initiated at 24 h post FPI in rats. Rats (n=8/group) were prepared for immunocytochemistry of GAD at 15 days post FPI.

Recovery of function after vagus nerve stimulation initiated 24 hours after fluid percussion brain injury.

Recent evidence from our laboratory demonstrated in laboratory rats that stimulation of the vagus nerve (VNS) initiated 2 h after lateral fluid percussion brain injury (FPI) accelerates the rate of recovery on a variety of behavioral and cognitive tests. VNS animals exhibited a level of performance comparable to that of sham-operated uninjured animals by the end of a 2-week testing period. The effectiveness of VNS was further evaluated in the present study in which initiation of stimulation was delayed until 24 h post-injury.

Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat.

The vagus nerve is an important source of afferent information about visceral states and it provides input to the locus coeruleus (LC), the major source of norepinephrine (NE) in the brain. It has been suggested that the effects of electrical stimulation of the vagus nerve on learning and memory, mood, seizure suppression, and recovery of function following brain damage are mediated, in part, by the release of brain NE. The hypothesis that left vagus nerve stimulation (VNS) at the cervical level results in increased extracellular NE concentrations in the cortex and hippocampus was tested at four stimulus intensities: 0.

Reeler homozygous mice exhibit enhanced susceptibility to epileptiform activity.

Purpose: Seizures are observed frequently in humans with diffuse neuronal migration disorders. The reeler mutant mouse also exhibits a diffuse disruption of migration, yet no pro-epileptic phenotype has been reported for this model. Whether this disparity reflects a phenotypic difference that can be used to delineate the mechanisms associated with increasing seizure susceptibility or reflects a paucity of knowledge is unclear.

Electrical stimulation of the vagus nerve enhances cognitive and motor recovery following moderate fluid percussion injury in the rat.

Intermittent, chronically delivered electrical stimulation of the vagus nerve (VNS) is an FDA-approved procedure for the treatment of refractory complex/partial epilepsy in humans. Stimulation of the vagus has also been shown to enhance memory storage processes in laboratory rats and human subjects. Recent evidence suggests that some of these effects of VNS may be due to the activation of neurons in the nucleus locus coeruleus resulting in the release of norepinephrine (NE) throughout the neuraxis.

The serotonergic and noradrenergic effects of antidepressant drugs are anticonvulsant, not proconvulsant.

Contrary to existing evidence, convulsant liability of the antidepressants has been attributed to noradrenergic and serotonergic increments. This is a classic case of confusing treatment effects with the manifestations of illness. In fact, the remarkable anticonvulsant effectiveness of antidepressant-induced noradrenergic and serotonergic activation has been ignored.

Brainstem seizure severity regulates forebrain seizure expression in the audiogenic kindling model.

Purpose: Although sound-induced (audiogenic) seizures in the genetically epilepsy-prone rat (GEPR) initially occur independent of the forebrain, repeated audiogenic seizures recruit forebrain seizure circuits in a process referred to as audiogenic kindling. In GEPR-3s, audiogenic kindling results in facial and forelimb (F&F) clonic seizures that are typical of forebrain seizures. However, in GEPR-9s, audiogenic kindling produces posttonic all-limb clonus not usually observed during forebrain seizures.

Weaving basic and social sciences into a case-based, clinically oriented medical curriculum: one school's approach.

Southern Illinois University School of Medicine recently completed its fourth year of a resource-session-enhanced, case-based, tutor-group-oriented curriculum. As an example of a curricular unit, the authors describe the implementation of the basic and clinical sciences in one of the four units in year one, and detail that unit's organization, logistics, content, rationale, and other characteristics. The Sensorimotor Systems and Behavior (SSB) unit is preceded by a cardio-respiratory-renal unit and is followed by an endocrine-reproductive-gastrointestinal unit.

Platelet monoamine oxidase B activity changes across 31 days of smoking abstinence.

Although recent studies demonstrate that tobacco cigarette smoke substantially inhibits both central nervous system and blood platelet monoamine oxidase (MAO) activity, little is known about the time course of MAO increases after smoking cessation. Therefore, changes in platelet MAO-B activity and mood were assessed before and at multiple times after quitting smoking. Quitting smoking was associated with a significant (22%) increase in MAO activity by day 3 and with a maximum increase (about 50%) by day 10 that was maintained through day 31 of abstinence.

Role of the superior colliculus and the intercollicular nucleus in the brainstem seizure circuitry of the genetically epilepsy-prone rat.

Purpose: The neuronal network responsible for the convulsive behavior associated with sound-induced seizures in genetically epilepsy-prone rats (GEPRs) is believed to include the inferior colliculus and other brainstem structures such as the deep layers of the superior colliculus (DLSC), periaqueductal gray, and pontine reticular formation. However, previous studies also suggested that the DLSC and the nearby intercollicular nucleus (ICN) are part of a midbrain anticonvulsant zone capable of suppressing tonic convulsions when activated with bicuculline. Our aim in this study was to investigate the role of the superior colliculus (SC) and the ICN in generalized tonic-clonic seizures (GTCSs).