Deletion of the vesicular monoamine transporter 1 (vmat1/slc18a1) gene affects dopamine signaling.

The vesicular monoamine transporter is involved in presynaptic catecholamine storage and neurotransmission. Two isoforms of the transporter exist, VMAT1 and VMAT2, and both are expressed in the brain, though VMAT2 expression is more robust and has been more widely studied. In this study we investigated the role of VMAT1 KO on markers of dopaminergic function and neurotransmission, and dopamine-related behaviors.

A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives.

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF-β family of ligands and are unequivocally involved in regulating stem cell behavior. Appropriate regulation of canonical BMP signaling is critical for the development and homeostasis of numerous human organ systems, as aberrations in the BMP pathway or its regulation are increasingly associated with diverse human pathologies. In this review, we provide a wide-perspective on strategies that increase or decrease BMP signaling.

Dexras1 a unique ras-GTPase interacts with NMDA receptor activity and provides a novel dissociation between anxiety, working memory and sensory gating.

Dexras1 is a novel GTPase that acts at a confluence of signaling mechanisms associated with psychiatric and neurological disease including NMDA receptors, NOS1AP and nNOS. Recent work has shown that Dexras1 mediates iron trafficking and NMDA-dependent neurodegeneration but a role for Dexras1 in normal brain function or psychiatric disease has not been studied. To test for such a role, mice with germline knockout (KO) of Dexras1 were assayed for behavioral abnormalities as well as changes in NMDA receptor subunit protein expression.

Corticosterone exposure augments sensitivity to the behavioral and neuroplastic effects of fluoxetine in C57BL/6 mice.

Both genetic background and pre-existing stress play critical roles in the effects of antidepressant drugs. The current studies showed this principal by demonstrating that exposure to the stress hormone corticosterone (CORT) allowed behavioral and neurogenic effects to emerge following chronic treatment with fluoxetine of C57BL/6 mice, a strain ordinarily resistant to these effects. Adult male mice were implanted subcutaneously with 21-day slow-release CORT pellets (10 mg) or placebo and then co-treated with 5 mg/kg fluoxetine (b.

Indomethacin reverses decreased hippocampal cell proliferation in streptozotocin-induced diabetic mice.

Diabetes in humans and animals is accompanied by chronic low-grade inflammation, which could be a possible mediator of developing neuropathology and neurobehavioral deficits. The objective of the present study determined if decreasing inflammation could reverse diabetes-induced decreases in hippocampal cell proliferation, one aspect of hippocampal neurogenesis. C57BL/6J mice were made diabetic by administering streptozotocin (STZ; 195 mg/kg).

High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice.

Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17days or a moderate high fat diet (HFD, 45% kcal by fat) for 8weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation.

Brain monoamines and antidepressant-like responses in MRL/MpJ versus C57BL/6J mice.

The MRL/MpJ mouse demonstrates enhanced wound healing and tissue regeneration and increased neurotrophic mobilization to chronic antidepressant drug treatments. This study compared brain monoamine systems between MRL/MpJ and C57BL/6J mice as a potential basis for strain differences after chronic antidepressant treatment. MRL/MpJ mice had significantly higher tissue levels of serotonin and dopamine in multiple brain regions.

VMAT1 deletion causes neuronal loss in the hippocampus and neurocognitive deficits in spatial discrimination.

Vesicular monoamine transporters (VMAT) are involved in presynaptic storage and release of neurotransmitters. While it was thought initially that only VMAT2 is brain expressed and VMAT1 is present only in the periphery, recent data have challenged the exclusive expression of VMAT2 in the brain. To further elucidate the role of VMAT1 brain expression and its potential role in neuropsychiatric disorders, we have investigated mice lacking VMAT1.

Strain differences in the effects of chronic corticosterone exposure in the hippocampus.

Stress hormones are thought to be involved in the etiology of depression, in part, because animal models show they cause morphological damage to the brain, an effect that can be reversed by chronic antidepressant treatment. The current study examined two mouse strains selected for naturalistic variation of tissue regeneration after injury for resistance to the effects of chronic corticosterone (CORT) exposure on cell proliferation and neurotrophin mobilization. The wound healer MRL/MpJ and control C57BL/6J mice were implanted subcutaneously with pellets that released CORT for 7 days.

Chronic methylphenidate administration in mice produces depressive-like behaviors and altered responses to fluoxetine.

Methylphenidate (MPH) is a psychostimulant used in the treatment of attention-deficit/hyperactivity disorder in children and adults. Increasing abuse rates of this drug have raised questions regarding the effects of chronic, high-dose MPH administration. Although the effects of chronic MPH exposure have been well-documented in regard to reward-related behaviors in adolescent and adult animals, there are few studies of the effects of MPH on depressive-like behaviors and antidepressant responses, particularly in adult models.

The transition between stochastic and deterministic behavior in an excitable gene circuit.

We explore the connection between a stochastic simulation model and an ordinary differential equations (ODEs) model of the dynamics of an excitable gene circuit that exhibits noise-induced oscillations. Near a bifurcation point in the ODE model, the stochastic simulation model yields behavior dramatically different from that predicted by the ODE model. We analyze how that behavior depends on the gene copy number and find very slow convergence to the large number limit near the bifurcation point.

Clinical presentations and molecular basis of complement C1r deficiency in a male African-American patient with systemic lupus erythematosus.

Homozygous deficiencies of early components for complement activation are among the strongest genetic risk factors for human systemic lupus erythematosus (SLE). Eleven cases of C1r deficiency are documented but this is the first report on the molecular basis of C1r deficiency. The proband is an African-American male who developed SLE at 3 months of age.

The hypocretin-orexin system regulates cocaine self-administration via actions on the mesolimbic dopamine system.

Recent evidence suggests that the hypocretin-orexin system participates in the regulation of reinforcement processes. The current studies examined the extent to which hypocretin neurotransmission regulates behavioral and neurochemical responses to cocaine, and behavioral responses to food reinforcement. These studies used a combination of fixed ratio, discrete trials, progressive ratio and threshold self-administration procedures to assess whether the hypocretin 1 receptor antagonist, SB-334867, reduces cocaine self-administration in rats.

Ethanol-induced hyperactivity is associated with hypodopaminergia in the 22-TNJ ENU-mutated mouse.

Characterization of neurochemical and behavioral responses to ethanol in phenotypically distinct mouse strains can provide insight into the mechanisms of ethanol stimulant actions. Increases in striatal dopamine (DA) levels have often been linked to ethanol-induced hyperactivity. We examined the functional status of the DA system and behavioral responsiveness to ethanol, cocaine, and a DA-receptor agonist in an N-ethyl-N-nitrosourea-mutagenized mouse strain, 22-TNJ, generated by the Integrative Neuroscience Initiative on Alcoholism Consortium.

Direct and indirect 5-HT receptor agonists produce gender-specific effects on locomotor and vertical activities in C57 BL/6J mice.

It is well established that the dopamine (DA) and serotonin (5-HT) systems have extensive and complex interactions. However, the effects of specific 5-HT receptor agonists on traditionally DA-related behaviors remain unclear. Our goal in these studies was to characterize the effects of 5-HT receptor agonists on measures of locomotor activity and vertical rearing.

Components of executive function in typically developing and head-injured children.

To identify the key components of executive functions (EFs) in children following traumatic brain injury (TBI), data from a series of EF tests administered to 286 pediatric TBI patients at least 3 years postinjury were subjected to an exploratory factor analysis. A 5-factor model included discourse, EFs (e.g.

Cognitive and linguistic correlates of children's discourse after closed head injury: a three-year follow-up.

The discourse of 91 children who had sustained severe (n = 68) or mild (n = 23) closed head injury (CHI) was examined at least three years postinjury. The groups' retellings of a narrative story were analyzed according to two domains, information and language. In comparison to the mild CHI group, the severe group produced stories characterized by reduced content and information, impaired organization, fewer words, and less complex sentences.

Memory functions in children with early hydrocephalus.

Children with arrested, shunted, and no hydrocephalus were compared on verbal and nonverbal memory tasks assessing multiple components of memory. A gradient of severity was hypothesized, with the shunted hydrocephalus group expected to exhibit the most significant memory impairments and the arrested group expected to perform more poorly than children with no hydrocephalus. Etiologies of prematurity, spina bifida, and aqueductal stenosis were represented by 157 participants.

On the surgical treatment of refractory epilepsy in tuberous sclerosis complex.

The role of surgery in the treatment of refractory epilepsy (RE) in tuberous sclerosis complex (TSC) is poorly defined. Four patients with RE and TSC were evaluated for epilepsy surgery from 1994 to 1996. Three of four patients developed infantile spasms within 5 months of birth.

Corpus callosotomy for medically intractable seizures.

To identify factors influencing outcome and morbidity in patients selected for corpus callosotomy, we retrospectively reviewed 23 patients with intractable generalized seizures who underwent corpus callosotomy between 1991 and 1994. Three patients had a complete corpus callosotomy, while 20 had an anterior callosotomy. Three of those patients subsequently had completion of the anterior callosotomy.

Quality of life perception in patients with intractable epilepsy or pseudoseizures.

Objectives: To contrast and compare self-reported quality of life in patients with intractable epilepsy and pseudoseizures and to examine the relationship between self-reports and objective measures of cognitive functioning in both of these groups.

Design: Case series using profile analysis and analysis of covariance.

Setting: University epilepsy surgery program.

Asymmetries in the effect of side of seizure onset on recognition memory following intracarotid amobarbital injection.

Purpose: To assess interhemispheric differences in recognition memory for objects during the intracarotid amobarbital sodium procedure (IAP).

Methods: The recognition memory for real objects of patients with either right (RTLE; n = 28) or left (LTLE; n = 22) temporal lobe epilepsy was assessed at baseline, and after left and right intracarotid amobarbital sodium injection.

Results: There were no differences between groups on baseline performance.