Anti-manic effect of deep brain stimulation of the ventral tegmental area in an animal model of mania induced by methamphetamine.

Background: Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD.

Lithium augmentation of ketamine increases insulin signaling and antidepressant-like active stress coping in a rodent model of treatment-resistant depression.

Lithium, a mood stabilizer and common adjunctive treatment for refractory depression, shares overlapping mechanisms of action with ketamine and enhances the duration of ketamine's antidepressant actions in rodent models at sub-therapeutic doses. Yet, in a recent clinical trial, lithium co-treatment with ketamine failed to improve antidepressant outcomes in subjects previously shown to respond to ketamine alone. The potential for lithium augmentation to improve antidepressant outcomes in ketamine nonresponders, however, has not been explored.

Mood Regulatory Actions of Active and Sham Nucleus Accumbens Deep Brain Stimulation in Antidepressant Resistant Rats.

The antidepressant actions of deep brain stimulation (DBS) are associated with progressive neuroadaptations within the mood network, modulated in part, by neurotrophic mechanisms. We investigated the antidepressant-like effects of chronic nucleus accumbens (NAc) DBS and its association with change in glycogen synthase kinase 3 (GSK3) and mammalian target of rapamycin (mTOR) expression in the infralimbic cortex (IL), and the dorsal (dHIP) and ventral (vHIP) subregions of the hippocampus of antidepressant resistant rats. Antidepressant resistance was induced via daily injection of adrenocorticotropic hormone (ACTH; 100 μg/day; 15 days) and confirmed by non-response to tricyclic antidepressant treatment (imipramine, 10 mg/kg).

Inflammatory Mechanisms in Parkinson's Disease: From Pathogenesis to Targeted Therapies.

Inflammation is a critical factor contributing to the progressive neurodegenerative process observed in Parkinson's disease (PD). Microglia, the immune cells of the central nervous system, are activated early in PD pathogenesis and can both trigger and propagate early disease processes via innate and adaptive immune mechanisms such as upregulated immune cells and antibody-mediated inflammation. Downstream cytokines and gene regulators such as microRNA (miRNA) coordinate later disease course and mediate disease progression.

Preventing Brain Injury in the Preterm Infant-Current Controversies and Potential Therapies.

Preterm birth is associated with a high risk of morbidity and mortality including brain damage and cerebral palsy. The development of brain injury in the preterm infant may be influenced by many factors including perinatal asphyxia, infection/inflammation, chronic hypoxia and exposure to treatments such as mechanical ventilation and corticosteroids. There are currently very limited treatment options available.

Ex Vivo MRI Analytical Methods and Brain Pathology in Preterm Lambs Treated with Postnatal Dexamethasone .

Postnatal glucocorticoids such as dexamethasone are effective in promoting lung development in preterm infants, but are prescribed cautiously due to concerns of neurological harm. We developed an analysis pipeline for post-mortem magnetic resonance imaging (MRI) to assess brain development and hence the neurological safety profile of postnatal dexamethasone in preterm lambs. Lambs were delivered via caesarean section at 129 days' (d) gestation (full term ≈ 150 d) with saline-vehicle control (Saline, = 9), low-dose tapered dexamethasone (cumulative dose = 0.

Physiological and anatomical investigation of the auditory brainstem in the Fat-tailed dunnart ().

The fat-tailed dunnart () is a small (10-20 g) native marsupial endemic to the south west of Western Australia. Currently little is known about the auditory capabilities of the dunnart, and of marsupials in general. Consequently, this study sought to investigate several electrophysiological and anatomical properties of the dunnart auditory system.

Targets of olivocochlear collaterals in cochlear nucleus of rat and guinea pig.

Descending auditory pathways can modify afferent auditory input en route to cortex. One component of these pathways is the olivocochlear system which originates in brainstem and terminates in cochlea. Medial olivocochlear (MOC) neurons also project collaterals to cochlear nucleus and make synaptic contacts with dendrites of multipolar neurons.

Differential responses to increasing numbers of mild traumatic brain injury in a rodent closed-head injury model.

Following mild traumatic brain injury (mTBI), further mild impacts can exacerbate negative outcomes. To compare chronic damage and deficits following increasing numbers of repeated mTBIs, a closed-head weight-drop model of repeated mTBI was used to deliver 1, 2 or 3 mTBIs to adult female rats at 24 h intervals. Outcomes were assessed at 3 months following the first mTBI.

The Effects of a Combination of Ion Channel Inhibitors in Female Rats Following Repeated Mild Traumatic Brain Injury.

Following mild traumatic brain injury (mTBI), the ionic homeostasis of the central nervous system (CNS) becomes imbalanced. Excess Ca influx into cells triggers molecular cascades, which result in detrimental effects. The authors assessed the effects of a combination of ion channel inhibitors (ICI) following repeated mTBI (rmTBI).

Vitamin D is crucial for maternal care and offspring social behaviour in rats.

Early life vitamin D plays a prominent role in neurodevelopment and subsequent brain function, including schizophrenic-like outcomes and increasing evidence for an association with autism spectrum disorder (ASD). Here, we investigate how early life vitamin D deficiency during rat pregnancy and lactation alters maternal care and influences neurodevelopment and affective, cognitive and social behaviours in male adult offspring. Sprague-Dawley rats were placed on either a vitamin D control (2195 IU/kg) or deficient diet (0 IU/kg) for five weeks before timed mating, and diet exposure was maintained until weaning of offspring on postnatal day (PND) 23.

Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma.

Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration.

Repeated mild traumatic brain injury in female rats increases lipid peroxidation in neurons.

Negative outcomes of mild traumatic brain injury (mTBI) can be exacerbated by repeated insult. Animal models of repeated closed-head mTBI provide the opportunity to define acute pathological mechanisms as the number of mTBI increases. Furthermore, little is known about the effects of mTBI impact site, and how this may affect brain function.

Delayed treatment of secondary degeneration following acute optic nerve transection using a combination of ion channel inhibitors.

Studies have shown that a combined application of several ion channel inhibitors immediately after central nervous system injury can inhibit secondary degeneration. However, for clinical use, it is necessary to determine how long after injury the combined treatment of several ion channel inhibitors can be delayed and efficacy maintained. In this study, we delivered Ca entry-inhibiting P2X7 receptor antagonist oxidized-ATP and AMPA receptor antagonist YM872 to the optic nerve injury site an iPRECIO pump immediately, 6 hours, 24 hours and 7 days after partial optic nerve transection surgery.

Vitamin D deficiency and impaired placental function: potential regulation by glucocorticoids?

Maternal vitamin D deficiency has been implicated in a range of pregnancy complications including preeclampsia, preterm birth and intrauterine growth restriction. Some of these adverse outcomes arise from alterations in placental function. Indeed, vitamin D appears critical for implantation, inflammation, immune function and angiogenesis in the placenta.

Effects of Neonatal Dexamethasone Exposure on Adult Neuropsychiatric Traits in Rats.

The effects of early life stress in utero or in neonates has long-term consequences on hypothalamic-pituitary-adrenal (HPA) stress axis function and neurodevelopment. These effects extend into adulthood and may underpin a variety of mental illnesses and be related to various developmental and cognitive changes. We examined the potential role of neonatal HPA axis activation on adult psychopathology and dopamine sensitivity in the mature rat using neonatal exposure to the synthetic glucocorticoid receptor agonist and stress hormone, dexamethasone.

Schizophrenia: the role of sleep and circadian rhythms in regulating dopamine and psychosis.

Schizophrenia has long been associated with abnormalities in circadian rhythms and sleep. Up until now, there have been no thorough reviews of the potential mechanisms behind the myriad of circadian and sleep abnormalities observed in schizophrenia and psychosis. We present evidence of sleep playing an important role in psychosis predominantly mediated by dopaminergic pathways.

The role of ephrin-A2 and ephrin-A5 in sensorimotor control and gating.

Many factors influence neurodevelopment. However, their contribution to adult neural function is often unclear. This is often due to complex expression profiles, cell signalling, neuroanatomy, and a lack of effective tests to assess the function of neural circuits in vivo.

Auditory brainstem responses of ephrin-A2, ephrin-A5(-/-) and ephrin-A2A5(-/-) mice.

Eph receptors and ephrin ligands are large families of cell surface proteins which have established roles in axonal growth and guidance. These are well characterized in the visual and somatosensory systems but are less well documented in the auditory pathway. We examined the possible functional role of two ephrin genes (ephrin-A2 and ephrin-A5) in the auditory system by measuring auditory brainstem responses (ABR) to tone bursts from 6 to 30 kHz in ephrin-A2(-/-), ephrin-A5(-/-) and ephrin-A2A5(-/-) (knockout) mice.