Key role for enkephalinergic tone in cortico–striatal–thalamic function

Abstract

Whereas the role of dopaminergic tone in the cortico-striatal-thalamic system is well-established, the role of endogenous opioids in the function of this system is less understood. We show that Borna disease virus infection of adult rats results in an increase in preproenkephalin transcripts in the striatum of Borna-infected rats, a region important for forming coordinated sequential motor actions and in developing programmes of thought and motivation. Stereotypic behaviours and dyskinesias, the clinical hallmarks of infection in adult Lewis rats (BD rats), are accompanied by a disrupted pattern of immediate early gene c-fos activation in the motor thalamus, with significance for the breakdown in coordinated sequential motor actions. We also find increased preproenkephalin in infected cultured neuroblastoma and rat foetal glial cells. The expression pattern of enkephalin mRNA in vivo and in vitro suggest that increased enkephalin function is one of the neuropharmacological means by which Borna disease virus causes motor disease of animals and possibly cognitive and affective disease in man, and further suggest that enkephalins play a critical role in the maintenance of a balanced tone of activity in the cortico-basal ganglia-thalamo-cortical loops.

A synthetic cannabinoid agonist promotes oligodendrogliogenesis during viral encephalitis in rats

“…In addition, BDV-infected BrdU + cells accounted for a small percentage of total cells in both BD and BD-WIN groups at the time point studied (striatum, 5% for BD and BD-WIN; PFC, 3% for BD and 4% for BD-WIN). As in previous reports (Gosztonyi and Ludwig, 1995; Solbrig et al, 2002), BDV nucleoprotein was detected in large neurons, such as striatal medium spiny neurons or PFC pyramidal neurons.…”

“…Microglia are activated by BDV infection of neurons (Ovanesov et al, 2006) and mixed inflammatory cells, mainly macrophages/microglia and CD8 + T cells, which produce CNS inflammation in adolescent or adult-infected rodents (Carbone et al, 1989; Deschl et al, 1990; Stitz et al, 2002; Solbrig et al, 2002; Solbrig et al, 2006). The CNS inflammation observed in BD differs, in this respect, from immune-mediated models of demyelinating diseases or MS, such as experimental allergic encephalomyelitis (EAE), a T cell-mediated autoimmune disease, and Theiler’s murine encephalomyelitis (TME), which is triggered by the mouse virus TMEV.…”

“…Adolescent rats experimentally infected with Borna Disease virus (BDV) develop a chronic microglial and inflammatory encephalitis (Hatalski et al, 1998; Solbrig et al, 2002; Stitz et al, 2002; Ovanesov et al, 2006) with frontostriatal injury producing stereotypical, perseverative and disinhibited dyskinetic behaviors (Solbrig et al, 1994). In rats, the adult rat medial PFC is equivalent to the human dorsolateral PFC (Gabbott et al, 2005) and, just as in humans, these cortices are functionally coupled to the striatum for the execution of planned behaviors and problem solving tasks (Dias-Ferreira et al, 2009).…”

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“…Local circuit interneurons of the dorsal striatum are also actively involved in regulating MSN activity (Gittis and Kreitzer, 2012) and can be subdivided into cholinergic interneurons (1-2% of all striatal cells) and aspiny GABAergic interneurons known as low-threshold, fast-spiking neurons (Lim et al, 2014). Striatal cholinergic and MSNs express several neurotransmitter receptors including the γ-aminobutyric acid (GABA), glutamate, DA, adenosine, serotonin, opioids, and substance P (NK1) receptors (Lee et al, 1997;Tzaferis and McGinty, 2001;Solbrig et al, 2002;Lim et al, 2014).…”

Stress Applied During Primary Immunization Affects the Secondary Humoral Immune Response in the Rat: Involvement of Opioid Peptides

“…Enkephalins are ligands for d opioid receptors that are widely distributed in the central (Mansour et al, 1988;Pan et al, 2002) and peripheral nervous system and are involved in numerous nervous functions (Solbrig et al, 2002). After stress, the content of messenger ribonucleic acid encoding enkephalin precursor significantly increases in discrete brain areas (Larsen and Mau, 1994;Wiedenmayer et al, 2002) and the concentration of enkephalins increases in the periphery (Parsons et al, 1990), suggesting involvement of d opioid receptor ligands in stress-induced physiological changes.…”