A Risk Factor for Attention Deficit Hyperactivity Disorder Induces Marked Long-Term Anatomical Changes at GABAergic-Dopaminergic Synapses in the Rat Ventral Tegmental Area.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. However, the core biology of the disorder that leads to the hypofunctioning of the cerebral dopaminergic network requires further elucidation. We investigated midbrain synaptic changes in male rats exposed to repeated hypoxia during the equivalent of extreme prematurity, which is a new animal model of the hyperactive/impulsive presentation of ADHD.

A Novel Rat Model of ADHD-like Hyperactivity/Impulsivity after Delayed Reward Has Selective Loss of Dopaminergic Neurons in the Right Ventral Tegmental Area.

In attention deficit hyperactivity disorder (ADHD), hyperactivity and impulsivity occur in response to reward. Herein we report a novel animal model in which male Sprague-Dawley rats exposed to repeated hypoxic brain injury during the equivalent of extreme prematurity were ADHD-like hyperactive/impulsive in response to delayed reward and attentive at 3 months of age. Thus, a unique animal model of one of the presentations/subtypes of ADHD was discovered.

Delayed Double Treatment with Adult-Sourced Adipose-Derived Mesenchymal Stem Cells Increases Striatal Medium-Spiny Neuronal Number, Decreases Striatal Microglial Number, and Has No Subventricular Proliferative Effect, after Acute Neonatal Hypoxia-Ischemia in Male Rats.

Perinatal hypoxia-ischemia (HI) is a major cause of striatal injury. Delayed post-treatment with adult-sourced bone marrow-derived mesenchymal stem cells (BMSCs) increased the absolute number of striatal medium-spiny neurons (MSNs) following perinatal HI-induced brain injury. Yet extraction of BMSCs is more invasive and difficult compared to extraction of adipose-derived mesenchymal stem cells (AD-MSCs), which are easily sourced from subcutaneous tissue.

A schizophrenia risk factor induces marked anatomical deficits at GABAergic-dopaminergic synapses in the rat ventral tegmental area: Essential evidence for new targeted therapies.

To develop new therapies for schizophrenia, evidence accumulated over decades highlights the essential need to investigate the GABAergic synapses that presynaptically influence midbrain dopaminergic neurons. Since current technology restricts these studies to animals, and evidence accumulated in recent decades indicates a developmental origin of schizophrenia, we investigated synaptic changes in male rat offspring exposed to maternal immune activation (MIA), a schizophrenia risk factor. Using a novel combination of lentiviruses, peroxidase-immunogold double labeling, three-dimensional serial section transmission electron microscopy and stereology, we observed clear anatomical alterations in synaptic inputs on dopaminergic neurons in the midbrain posterior ventral tegmental area (pVTA).

Postnatal expression of thalamic GABAA receptor subunits in the stargazer mouse model of absence epilepsy.

Absence seizures are known to originate from disruptions within the corticothalamocortical network; however, the precise underlying cellular and molecular mechanisms that induce hypersynchronicity and hyperexcitability are debated and likely to be complex and multifactorial. Recent studies implicate impaired thalamic GABAergic inhibition as a common feature in multiple animal models of absence epilepsy, including the well-established stargazer mouse model. Recently, we demonstrated region-specific increases in the whole tissue and synaptic levels of GABAA receptor (GABAAR) subunits α1 and β2, within the ventral posterior region of the thalamus in adult epileptic stargazer mice compared with nonepileptic control littermates.

Altered thalamic GABAA-receptor subunit expression in the stargazer mouse model of absence epilepsy.

Purpose: Absence seizures, also known as petit mal seizures, arise from disruptions within the cortico-thalamocortical network. Interconnected circuits within the thalamus consisting of inhibitory neurons of the reticular thalamic nucleus (RTN) and excitatory relay neurons of the ventral posterior (VP) complex, generate normal intrathalamic oscillatory activity. The degree of synchrony in this network determines whether normal (spindle) or pathologic (spike wave) oscillations occur; however, the cellular and molecular mechanisms underlying absence seizures are complex and multifactorial and currently are not fully understood.