Neuroscience
-
Comparative Study
Increased expression of Ca2+/calmodulin-dependent protein kinase II alpha during chronic morphine exposure.
The chronic administration of morphine and related opioid drugs results in tolerance and dependence which limits the clinical utility of these agents. Neuronal plasticity is probably responsible in large part for tolerance and dependence. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a crucial role in the neuroplastic events underlying memory formation and other phenomena. ⋯ In addition, the abundance of phosphorylated CaMKIIalpha was increased in spinal cord tissue from morphine-treated mice. We conclude that enhanced CaMKIIalpha expression and activity in spinal cord tissue may contribute to the development of morphine tolerance in mice. The involvement of this enzyme in opioid tolerance suggests other parallels may exist between the neuroplastic events related to memory formation and those related to opioid tolerance or pain.
-
Although gender differences in the response to stress have been reported, differences in stress-induced changes in feeding behavior have not been well studied. In this report, inhibition of food intake was compared in male and female rats following 1 h of restraint, electric footshock, or emotional stress induced by a communication box. Although the three stressors inhibited food intake in both genders, only emotional stress caused a gender difference, a greater inhibition of food intake in female rats (48%) than in male rats (22%). ⋯ Ovariectomy reduced the inhibition of food intake by emotional stress to the same level as that in male, and replacement with estradiol restored the inhibition to the level of the normal female rats. A corticotropin-releasing factor (CRF) type 1 receptor antagonist prevented emotional stress-induced inhibition of food intake, indicating the involvement of CRF type 1 receptor in emotional stress-induced inhibition of food intake. These results suggest that female rats show a greater inhibition of food intake in response to emotional stress than male rats and that estrogen plays a role in the gender difference.
-
We have previously shown that voluntary exercise produces enhanced neurogenesis and long-term potentiation (LTP) in the dentate gyrus (DG) of mice in vitro. In the present experiments we show that rats given access to a running wheel (Runners) exhibit significantly more short-term potentiation and LTP with theta-patterned conditioning stimulation in vivo than do age-matched litter mates (Controls). This increase in LTP appears to reflect an alteration in the induction threshold for synaptic plasticity that accompanies voluntary exercise. ⋯ Consistent with these findings, we found that mRNA levels for NR2B subtype of NMDA receptor were increased specifically in the DG of Runners. In addition to changes in NR2B mRNA levels, quantitative polymerase chain reaction analysis revealed that brain-derived neurotrophic factor (BDNF) and glutamate receptor 5 mRNA levels were also significantly elevated in the DG of Runners, but not in other areas of the hippocampus. Thus, alterations in the expression of BDNF, and specific glutamate receptor subtypes, may underlie the ability of exercise to enhance neurogenesis and reduce the threshold for LTP in the DG.
-
The amygdala and hippocampus are key limbic structures of the temporal lobe, and are implicated in the pathology of mood disorders. Bcl-2, an intracellular protein, has recently been identified in the primate amygdala and hippocampus, and is now recognized as an intracellular target of mood stabilizing drugs. However, there are few data on the cellular phenotypes of bcl-2-expressing cells, or their distribution in specific subregions of the amygdala and hippocampus. ⋯ Bcl-2 is thus important in intrinsic circuitry of the hippocampus, and in amygdaloid subregions modulated by the hippocampus. In addition, the extended amygdala, a key amygdaloid output, is richly endowed with bcl-2 positive cells. This distribution suggests a role for bcl-2 in circuits mediating emotional learning and memory which may be targets of mood stabilizing drugs.
-
Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury (TBI) as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist: "vasogenic" due to blood-brain barrier (BBB) disruption resulting in extracellular water accumulation and "cytotoxic/cellular" due to sustained intracellular water collection. A third type, "osmotic" brain edema is caused by osmotic imbalances between blood and tissue. ⋯ For many years, vasogenic brain edema was accepted as the prevalent edema type following TBI. The development of mechanical TBI models ("weight drop," "fluid percussion injury," and "controlled cortical impact injury") and the use of magnetic resonance imaging, however, revealed that "cytotoxic" edema is of decisive pathophysiological importance following TBI as it develops early and persists while BBB integrity is gradually restored. These findings suggest that cytotoxic and vasogenic brain edema are two entities which can be targeted simultaneously or according to their temporal prevalence.