Chronic (–)-Deprenyl Administration Attenuates Dendritic Developmental Impairment Induced by Early Social Isolation in the Rat

Abstract

It has been demonstrated that postweaning social isolation alters dendritic development in the medial prefrontal cortex (mPFC) of the rat. In addition, (–)-deprenyl, a monoamine oxidase B (MAO-B) inhibitor, promotes dendritic growth in prefrontocortical pyramidal cells. This study examined whether prefrontocortical dendritic developmental impairment induced by postweaning social isolation is attenuated by chronic (–)-deprenyl administration. Weanling Sprague-Dawley male rats were randomly reared in social and isolated environments between postnatal days 21 and 51 (P21–P51). At P52, half of the animals were behaviorally evaluated in the open-field test and sacrificed for histological analysis. The remaining isolated rats were subdivided into saline- and daily (–)-deprenyl-treated animals for 30 additional days (P52–P82). Socially-reared rats remained undisturbed except for daily saline administration. At P82, all animals were behaviorally evaluated and sacrificed for histological analysis. Dendritic quantification of the Golgi-Cox-Sholl-stained neurons indicated that chronic (–)-deprenyl administration partially compensated the dendritic growth impairment induced by social isolation. In addition, both isolated-saline- and (–)-deprenyl-treated rats showed a sustained locomotor hyperactivity in the open-field test.

Selegiline (deprenyl) decreases calbindin‐D28k expression in cortical neurons of rats socially deprived during the post‐weaning period

“…In addition, it has been shown that SEL promotes dendritic outgrowth in frontal, hippocampal, mesencephalic and spinal neurons (Iwasaki et al, 1994;Kontkanen and Castrén, 1999;Lakshmana et al, 1998;Shankaranarayana-Rao et al, 1999), suggesting trophic-like actions. Likewise, in a previous study we were able to demonstrate that SEL can partially recover cortical dendritic outgrowth impairments induced by post-weaning isolation stress (Pascual and Zamora-León, 2007).…”

“…On the other hand, lower expression of CB in the cerebral cortices of animals treated with SEL suggest that at least one of the neuroprotective effects of selegiline occurs through the increased efficiency of target neurons in buffering Ca 2+ overload, as indirectly evidenced by CB down‐regulation. In the current study, we used a dose of SEL (0.2 mg kg −1 ) that, as shown in previous works, produced neurotrophic and neuroprotective effects (Kontkanen and Castrén, 1999; Lakshmana et al, 1998; Shankaranarayana‐Rao et al, 1999; Pascual and Zamora‐León, 2007). Considering the neuroprotective and neurotrophic effects of SEL described in previous studies, we believe that SEL should not be dismissed as a potent neuroprotective drug without an exhaustive assessment of its dose‐related effects.…”

“…(Sigma–Aldrich) dissolved in 2 ml saline (0.9% NaCl; 8:00 h p.m.). The dose of SEL and the treatment duration were selected based on neuroprotective and trophic effects reported in previous studies (Foley et al, 2000; Heinonen and Lammintausta, 1991; Pascual and Zamora‐León, 2007). SI‐SAL and SC‐SAL animals received vehicle in a similar volume.…”

Animal models of schizophrenia

“…Several of the neurobiological changes in the brain of isolation‐reared rats resemble those seen in the schizophrenic patient, hence the model has good construct validity. For example, as in schizophrenic patients (Hirayasu et al ., 2001; Harrison, 2004), a selective reduction in PFc volume occurs in isolation‐reared rats (Day‐Wilson et al ., 2006; Schubert et al ., 2009) accompanied by decreased dendritic spine density and morphology (Silva‐Gomez et al ., 2003; Pascual and Zamora‐Leon, 2007), cytoskeletal alterations (Bianchi et al ., 2006) and reduced parvalbumin and calbindin‐containing GABAergic chandelier cartridges (Harte et al ., 2007; Bloomfield et al ., 2008) of hippocampal and PFc interneurones. The age of commencing isolation rearing and gender both interact to affect the extent of change in dendritic spine morphology and complexity that develops in PFc, anterior cingulate and orbitofrontal cortices (Ferdman et al ., 2007).…”

Remodeling of axo-spinous synapses in the pathophysiology and treatment of depression

“…Chronic administration of another MAOI (−)-deprenyl prevents the dendritic impairments of rat PFC pyramidal neurons caused by social isolation stress (Pascual and Zamora-Leon, 2007). In a very recent study rats treated for 10 days with 9-Methyl- β -carboline, which inhibits MAO-A but also has other effects on monoamine transmission, improved spatial learning in the radial maze and increased dendrite complexity and spine number on dentate gyrus granule cells (Gruss et al, 2012).…”