A solution-hybridization ribonuclease-protection assay was used to identify epidermal growth factor (EGF) mRNA in mouse brain and to compare the regional and developmental levels of EGF gene expression in the CNS with those of its structural homolog, transforming growth factor-alpha (TGF-alpha). Adult brain regions examined included brainstem, cerebellum, cerebral cortex, hippocampus, basal hypothalamus, olfactory bulb, olfactory tubercle, striatum, and thalamus. While both EGF and TGF-alpha mRNAs were detected in all regions, TGF-alpha mRNA levels were 15-170 times higher, ranging from 0.39 (cerebellum and cerebral cortex) to 2.93 (striatum) pg TGF-alpha mRNA/micrograms total cytoplasmic RNA. In contrast, EGF mRNA levels ranged from 11 to 36 fg EGF mRNA/micrograms, with the highest regional concentrations observed in olfactory bulb, basal hypothalamus, and cerebellum. In our comparison between sexes, no significant male-female differences in EGF or TGF-alpha mRNA levels were observed for any region of adult brain. However, in the pituitary gland, consisting of both endocrine and neural elements, EGF and TGF-alpha mRNA levels were significantly higher in males (234 and 215 fg/micrograms, respectively) than in females (172 and 118 fg/micrograms, respectively). An examination of growth factor gene expression in the developing CNS revealed EGF and TGF-alpha mRNAs detectable as early as embryonic day 14 (earliest time point studied). While gene expression for both peptides continued into the postnatal period, EGF and TGF-alpha mRNA levels were nearly equal to adult concentrations by postnatal day 10. Taken together, our findings provide evidence for the synthesis of EGF in brain and suggest a role for both EGF and TGF-alpha in the development and support of the mammalian CNS.
Summary:Purpuse: Antiepileptic drugs (AEDs) are frequently used for their beneficial psychoactive effects on affective disorders. We sought to demonstrate a psychoactive effect of gabapentin (GBP) when used as add-on AED therapy.Methods: Forty adult patients with partial epilepsy were studied in a prospective, non-randomized fashion with interviewerrated and self-rated scales of mood and anxiety: the Cornell Dysthymia Rating Scale (CDRS), Beck Depression Inventory (BDI), and Hamilton Depression (Ham-D) and Anxiety (Ham-A) Scales. After completion of baseline mood and anxiety scales (time l ) , 20 of the 40 patients were prescribed add-on GBP (treated group). The remaining 20 patients served as a control group. Both groups were similar in age and sex distribution. Follow-up mood and anxiety scales were performed in all patients -3 months later (time 2). The average GBP dose at time 2 was 1,615 mg/day. All patients were taking stable doses Patients with epilepsy experience interictal depression more than any other mood disorder (1). Features of depression and anxiety are frequently evident in such patients even if formal diagnostic criteria for a psychiatric disorder are not met. For example, Robertson et al. (2) reported a series of patients with temporal lobe epilepsy (TLE) with significantly greater depressive and anxietyrelated symptoms compared with controls. However, the patients with TLE failed to meet DSM-111-R criteria for a major depressive disorder 75% of the time (2).Blumer et al. (3) described an atypical mood disorder in one-third of patients with epilepsy admitted for neurodiagnostic monitoring. This mood disorder was characterized by depressed mood, anergia, irritability, episodic euphoria, atypical pain, insomnia, and phobias. of one to four AEDs at baseline and throughout the study. Seizure frequency was monitored throughout. Statistical significance was assessed by analysis of variance (ANOVA) by using a two-factor repeated-measures model.Results: The GBP-treated group had a significant decrease in CDRS score over time compared with the control group (p = 0.04). No significant differences between the control and the treated groups were found for any of the remaining mood scales (BDI, p = 0.58; Ham-D, p = 0.59; Ham-A, p = 0.93). There was no significant difference or change in seizure frequency between groups.Conclusions: GBP treatment is associated with mood improvement as measured by the CDRS. This improvement was not accounted for by seizure improvement.
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