Dissociation between mossy fiber sprouting and rapid kindling with low-frequency stimulation of the amygdala

It has been proposed that antidepressants have neuroprotective effects on hippocampal neurons. To further test this hypothesis, brainderived neurotrophic factor (BDNF), B cell lymphoma protein-2 (Bcl-2), and copper-zinc superoxide dismutase (Cu/Zn-SOD) were examined immunohistochemically in hippocampal neurons of Sprague-Dawley rats following daily treatment with 5 or 10 mg/kg of amitriptyline or venlafaxine for 21 days. At 5 mg/kg, both amitriptyline and venlafaxine increased the intensity of BDNF immunostaining in hippocampal pyramidal neurons, and the intensity of Bcl-2 immunostaining in hippocampal mossy fibers, but did not alter the Cu/Zn-SOD immunoreactivity. The high dose of venlafaxine, however, decreased the intensity of BDNF immunostaining in all subareas of the hippocampus and increased the intensity of Cu/Zn-SOD immunostaining in the dentate granular cell layer. The high dose of amitriptyline increased the intensity of Cu/Zn-SOD immunostaining, but did not affect the immunoreactivity of Bcl-2 or BDNF. These findings suggest that the chronic administration of amitriptyline or venlafaxine at 5 mg/kg, but not 10 mg/kg, may be neuroprotective to hippocampal neurons. These dose-related effects of antidepressant drugs on hippocampal neurons may have relevance to disparate findings in the field.

show abstract

“…Furthermore, a percentage difference score (DS) in optical density was calculated according to the following formula (Armitage et al, 1998):…”

Section: Densitometric Analysismentioning

confidence: 99%

Dose-Related Effects of Chronic Antidepressants on Neuroprotective Proteins BDNF, Bcl-2 and Cu/Zn-SOD in Rat Hippocampus

Richardson

2003

Neuropsychopharmacol

157

View full text Add to dashboard Cite

show abstract

“…Several previous studies have demonstrated kindling-induced morphological alterations at the cellular, dendritic, and synaptic level in the hippocampus (Armitage et al, 1998;Binder et al, 1999;Cavazos et al, 1994;Cavazos and Sutula, 1990;Geinisman et al, 1988Geinisman et al, , 1990Geinisman et al, , 1992Hawrylak et al, 1993;Hovorka et al, 1997;Jiang et al, 1998;Mohapel et al, 2000;Spiller and Racine, 1994;Sutula, 1990), amygdala (Nishizuka et al, 1991;Okada et al, 1993), and neocortex (Teskey et al, 1999(Teskey et al, , 2001. The two later studies that examined dendritic alterations in the neocortex following kindling focused on layer III pyramidal cells because earlier work had shown a sexual dimorphism at the structural level (Kolb and Stewart, 1991) and a differential plastic response to midline frontal lesions (Kolb and Whishaw, 1991) and gonadal hormones (Kolb and Stewart, 1995) in that layer.…”

Section: Introductionmentioning

confidence: 99%

Neocortical kindling is associated with opposing alterations in dendritic morphology in neocortical layer V and striatum from neocortical layer III

Teskey

Monfils

Silasi

et al. 2005

Synapse

View full text Add to dashboard Cite

Previous research has shown that seizures kindled in the corpus callosum result in a persistent enhancement of the callosal-neocortical evoked response but only a transient reduction in layer III pyramidal cell morphology. To date, there are no reports on the direct effects of repeated seizures on dendritic morphology in layer V, the pyramidal layer thought to mediate the kindling-induced enhanced evoked response. This experiment examined the effect of repeated seizures elicited from the corpus callosum, at the level of the frontal neocortex, on the morphology of sensorimotor frontal (Fr1) and occipital (OC1) neocortical layer V, as well as striatal and neuronal dendrites, in male rats. After 25 days of electrically elicited seizures or handling control, rats were sacrificed either 2 days or 3 weeks following the last seizure and processed for Golgi-Cox staining. Analysis of the impregnated pyramidal cell dendrites indicated a significant increase in the amount of dendritic length and branching in rats 2 days, but a decrease 3 weeks, following the last seizure. There was no effect at the distant occipital site. The differential effect between layer V pyramidal neurons and layer III pyramidal neurons suggests that these areas play different roles in the expression of seizures and the adaptation of the brain to the persistent effect of kindling.

show abstract

“…The work from our own laboratory with the use of a protein synthesis inhibitor, cycloheximide (CHX), to block MFS in the IML after induction of status epilepticus in rats (21-23) is only one approach to the subject (24)(25)(26). The basic message from these papers is that epileptogenesis may develop in the absence of MFS in the IML.…”

mentioning

confidence: 99%

The Role of Mossy Cell Death and Activation of Protein Synthesis in the Sprouting of Dentate Mossy Fibers: Evidence from Calretinin and Neo‐Timm Staining in Pilocarpine‐Epileptic Mice

Silva¹,

Mello²

2000

Epilepsia

View full text Add to dashboard Cite

Summary:Mossy fiber sprouting is a major anatomical reorganization seen in patients with temporal lobe epilepsy and animal models of epilepsy. The final outcome of this reorganization is viewed by many as epileptogenic. Yet, important and relevant data from both human and animal models of epilepsy challenge this prevailing view. Regardless of the outcome of this debate, understanding of the mechanisms that underlie mossy fiber sprouting (MFS) might contribute to our understanding of both the adaptive and maladaptive changes that take place in the nervous system after injury. Available evidence suggests that two events might be crucial for mossy fibers to sprout in epilepsy: the death of mossy cells and the synthesis of trophic factors. The availability of means that prevent MFS, which is normally triggered after induction of status epilepticus, allow for the testing of hypotheses regarding the need for and the sufficiency of specific events for mossy fibers to sprout.We present data on a specific marker for mossy cells, calretinin, in the pilocarpine model of epilepsy in mice. Our data suggest that in the presence of a protein synthesis inhibitor status epilepticus-induced death of mossy cells is not sufficient to trigger mossy fiber sprouting. We suggest that both events, mossy cell death and synthesis of trophic factors, might be necessary for robust MFS to ensue. Key Words: Status epilepticus-Mossy fiber sprouting-Mossy cells-Dentate gyrus-Granule cells-GAP-43-Hippocampus-Temporal lobe epilepsy-Synaptic reorganization.It is becoming evident that temporal lobe epilepsy (TLE) is not a single pathological entity but rather might encompass many different pathologies and thus may be associated with various pathophysiologies. A good example of this plural side of the TLEs is the sprouting of the axons of granule cells onto the inner molecular layer (IML) of the dentate gyrus. These axons, the mossy fibers, which are not normally present in the IML of humans or of most other animals without epilepsy, might be conspicuously present in humans with TLE and animal models of epilepsy (1-5). Yet, it is clear that in some forms of TLE, there is little or no mossy fiber sprouting (MFS). According to a classification of TLE based on tissue analysis (6), both medial TLEs associated with mass lesions (tumors) and paradoxical medial TLEs might not present MFS.After the seminal demonstration of MFS in the IML in tissue from animal models of TLE (5), this form of synAddress correspondence and reprint requests to Dr. Luiz E. A. M. Mello at Department of Physiology, UNIFESP, Rua Botucatu 862, 04023-900 S2o Paulo, SP Brazil. E-mail: lemello@ecb.epm.br aptic reorganization has been demonstrated in almost every epileptic condition, even those not clearly associated with the temporal lobe (7). Despite the extensive demonstration of its presence in tissue from epilepsy patients and the clear theoretical background in favor of its role in epileptogenesis (8-1 7), the relevance of MFS to epileptic seizures remains a controversial issue. T...

show abstract

Dissociation between mossy fiber sprouting and rapid kindling with low-frequency stimulation of the amygdala

Cited by 26 publications

References 46 publications

Dose-Related Effects of Chronic Antidepressants on Neuroprotective Proteins BDNF, Bcl-2 and Cu/Zn-SOD in Rat Hippocampus

Dose-Related Effects of Chronic Antidepressants on Neuroprotective Proteins BDNF, Bcl-2 and Cu/Zn-SOD in Rat Hippocampus

Neocortical kindling is associated with opposing alterations in dendritic morphology in neocortical layer V and striatum from neocortical layer III

The Role of Mossy Cell Death and Activation of Protein Synthesis in the Sprouting of Dentate Mossy Fibers: Evidence from Calretinin and Neo‐Timm Staining in Pilocarpine‐Epileptic Mice

Contact Info

Product

Resources

About