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Acta Neurobiologiae Experimentalis 1994A review of the literature concerning cholinergic manipulations and passive avoidance reveals that state-dependency is usually not controlled adequately, nor is... (Review)
Review
A review of the literature concerning cholinergic manipulations and passive avoidance reveals that state-dependency is usually not controlled adequately, nor is acquisition of the passive avoidance task ascertained before retention is tested. These problems make interpretation of results difficult. We report three experiments on 129 rats, controlling both of these factors, in which scopolamine and pilocarpine impaired both acquisition and retention of a passive avoidance response. Lesions of the nucleus basalis magnocellularis had no effect on this task. The results suggest that an optimal level of central cholinergic activity exists for learning and memory, and that deviations from this optimal level impair acquisition and retention.
Topics: Acetylcholine; Animals; Avoidance Learning; Brain; Mental Recall; Pilocarpine; Rats; Rats, Sprague-Dawley; Scopolamine
PubMed: 7887188
DOI: No ID Found -
Brazilian Journal of Biology = Revista... 2022Epilepsy is one of the most common neurological disorders affecting most social, economic and biological aspects of human life. Most patients with epilepsy have...
Epilepsy is one of the most common neurological disorders affecting most social, economic and biological aspects of human life. Most patients with epilepsy have uncontrolled seizures and drug side effects despite the medications. Patients with epilepsy often have problems with attention, memory, and information processing speed, which may be due to seizures, underlying causes, or anticonvulsants. Therefore, improving seizure control and reducing or changing the anti-epileptic drugs can solve these problems, but these problems will not be solved in most cases. In this work, we looked at the effects of pioglitazone, a Peroxisome Proliferator-Activated Receptor agonist used to treat type 2 diabetes, on pilocarpine-induced seizures in mice. The Racine scale was used to classify pilocarpine-induced convulsions. After that, all of the animals were beheaded, and the brain and hippocampus were dissected. Finally, biochemical techniques were used to determine the levels of Malondialdehyde and Catalase activity, as well as Superoxide Dismutase and Glutathione Reductase in the hippocampus. The results of this investigation suggest that pioglitazone's antioxidant action may play a key role in its neuroprotective properties against pilocarpine-induced seizure neuronal damage.
Topics: Animals; Antioxidants; Diabetes Mellitus, Type 2; Epilepsy; Humans; Male; Mice; Pilocarpine; Pioglitazone; Seizures
PubMed: 35584460
DOI: 10.1590/1519-6984.260091 -
Brain Stimulation 2019Temporal lobe epilepsy is most prevalent among focal epilepsies, and nearly one-third of patients are refractory to pharmacological intervention. Persistent cognitive...
BACKGROUND
Temporal lobe epilepsy is most prevalent among focal epilepsies, and nearly one-third of patients are refractory to pharmacological intervention. Persistent cognitive and neurobehavioral comorbidities also occur due to the recurrent nature of seizures and medication-related side effects.
HYPOTHESIS
Electrical neuromodulation is an effective strategy to reduce seizures both in animal models and clinically, but its efficacy to modulate cognition remains unclear. We hypothesized that theta frequency stimulation of the medial septum would increase septohippocampal oscillations, increase seizure threshold, and improve spatial learning in a rat model of pilocarpine-induced epilepsy.
METHODS
Sham and pilocarpine rats were implanted with electrodes in the medial septum, hippocampus and prefrontal cortex. EEG was assessed days prior to and following stimulation. Sham and pilocarpine-treated rats received either no stimulation, continuous (throughout each behavior), or pre-task (one minute prior to each behavior) 7.7 Hz septal stimulation during the Barnes maze spatial navigation test and also during assessment of flurothyl-induced seizures.
RESULTS
Both continuous and pre-task stimulation prevented epilepsy-associated reductions in theta oscillations over time. Additionally, both stimulation paradigms significantly improved spatial navigation in the Barnes maze, reducing latency and improving search strategy. Moreover, stimulation led to significant increases in seizure threshold in pilocarpine-treated rats. There was no evidence of cognitive enhancement or increased seizure threshold in stimulated sham rats.
CONCLUSION
These findings have profound implications as theta stimulation of the septum represents a single frequency and target that has the potential to both improve cognition and reduce seizures for patients with refractory epilepsy.
Topics: Animals; Cognition; Deep Brain Stimulation; Epilepsy, Temporal Lobe; Hippocampus; Male; Pilocarpine; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Spatial Learning; Theta Rhythm
PubMed: 30733144
DOI: 10.1016/j.brs.2019.01.005 -
Epilepsy & Behavior : E&B Aug 2021In rodents, status epilepticus (SE) triggered by chemoconvulsants can differently affect the proliferation and fate of adult-born dentate granule cells (DGCs). It is...
In rodents, status epilepticus (SE) triggered by chemoconvulsants can differently affect the proliferation and fate of adult-born dentate granule cells (DGCs). It is unknown whether abnormal neurogenesis results from intracellular signaling associated with drug-receptor interaction, paroxysmal activity, or both. To test the contribution of these factors, we systematically compared the effects of kainic acid (KA)- and pilocarpine (PL)-induced SE on the morphology and localization of DGCs generated before or after SE in the ipsi- and contralateral hippocampi of mice. Hippocampal insult was induced by unilateral intrahippocampal (ihpc) administration of KA or PL. We employed conditional doublecortin-dependent expression of the green fluorescent protein (GFP) to label adult-born cells committed to neuronal lineage either one month before (mature DGCs) or seven days after (immature DGCs) SE. Unilateral ihpc administration of KA and PL led to bilateral epileptiform discharges and focal and generalized behavioral seizures. However, drastic granule cell layer (GCL) dispersion occurred only in the ipsilateral side of KA injection, but not in PL-treated animals. Granule cell layer dispersion was accompanied by a significant reduction in neurogenesis after SE in the ipsilateral side of KA-treated animals, while neurogenesis increased in the contralateral side of KA-treated animals and both hippocampi of PL-treated animals. The ratio of ectopic neurons in the ipsilateral hippocampus was higher among immature as compared to mature neurons in the KA model (32.8% vs. 10.0%, respectively), while the occurrence of ectopic neurons in PL-treated animals was lower than 3% among both mature and immature DGCs. Collectively, our results suggest that KA- and PL-induced SE leads to distinct cellular alterations in mature and immature DGCs. We also show different local and secondary effects of KA or PL in the histological organization of the adult DG, suggesting that these unique epilepsy models may be complementary to our understanding of the disease. NEWroscience 2018.
Topics: Animals; Dentate Gyrus; Disease Models, Animal; Hippocampus; Mice; Neurogenesis; Pilocarpine; Status Epilepticus
PubMed: 31704249
DOI: 10.1016/j.yebeh.2019.106575 -
Revista Brasileira de Parasitologia... Jun 2016The aim of this study was to assess the activity of aqueous (AE) and ethanolic extracts (EE) and pilocarpine hydrochloride, which were extracted and isolated from...
The aim of this study was to assess the activity of aqueous (AE) and ethanolic extracts (EE) and pilocarpine hydrochloride, which were extracted and isolated from Pilocarpus microphyllus (Jaborandi), respectively, on Rhipicephalus (Boophilus) microplus. High performance liquid chromatography (HPLC) was performed to quantify these compounds. Larval packet and adult immersion tests were conducted with different concentrations. Five AE and EE concentrations, ranging from 6.2 to 100.0 mg mL-1, and six concentrations of pilocarpine hydrochloride, ranging from 0.7 to 24.0 mg mL-1, were tested. The lethal concentration (LC50) of each extract for larvae and engorged females was calculated through Probit analysis. The concentration of pilocarpine hydrochloride obtained from the EE and the AE was 1.3 and 0.3% (m/m), respectively. Pilocarpine hydrochloride presented the highest acaricidal activity on larvae (LC50 2.6 mg mL-1) and engorged females (LC50 11.8 mg mL-1) of R.(B.) microplus, followed by the EE which presented LC50 of 56.4 and 15.9 mg mL-1, for larvae and engorged females, respectively. Such results indicate that pilocarpine hydrochloride has acaricidal activity, and may be the primary compound responsible for this activity by P. microphyllus EE.
Topics: Acaricides; Animals; Female; Larva; Lethal Dose 50; Pilocarpine; Pilocarpus; Plant Extracts; Rhipicephalus
PubMed: 27334829
DOI: 10.1590/S1984-29612016032 -
The Journal of Neuroscience : the... Apr 2022Hilar mossy cells regulate network function in the hippocampus through both direct excitation and di-synaptic inhibition of dentate granule cells (DGCs). Substantial...
Hilar mossy cells regulate network function in the hippocampus through both direct excitation and di-synaptic inhibition of dentate granule cells (DGCs). Substantial mossy cell loss accompanies hippocampal circuit changes in epilepsy. We examined the contribution of surviving mossy cells to network activity in the reorganized dentate gyrus after pilocarpine-induced status epilepticus (SE). To examine functional circuit changes, we optogenetically stimulated mossy cells in acute hippocampal slices from male mice. In control mice, activation of mossy cells produced monosynaptic excitatory and di-synaptic GABAergic currents in DGCs. In pilocarpine-treated mice, mossy cell density and excitation of DGCs were reduced in parallel, with only a minimal reduction in feedforward inhibition, enhancing the inhibition/excitation ratio. Surprisingly, mossy cell-driven excitation of parvalbumin-positive (PV+) basket cells, primary mediators of feed-forward inhibition, was maintained. Our results suggest that mossy cell outputs reorganize following seizures, increasing their net inhibitory effect in the hippocampus. Hilar mossy cell loss in epilepsy is associated with hippocampal hyperexcitability, potentially as a result of disrupted dentate microcircuit function. We used transgenic mice, translational mouse modeling, viral vectors, and optogenetics to selectively examine functional changes to mossy cell outputs following status epilepticus (SE). Interestingly, the outputs of surviving mossy cells exhibited adaptive plasticity onto target parvalbumin-positive (PV+) interneurons, resulting in a relative increase in their inhibitory control of dentate granule cells (DGCs). Our findings suggest that residual mossy cell outputs can reorganize in a homeostatic manner, which may provide clues for therapeutic targeting of this microcircuit.
Topics: Adaptation, Physiological; Animals; Dentate Gyrus; Male; Mice; Mossy Fibers, Hippocampal; Parvalbumins; Pilocarpine; Status Epilepticus
PubMed: 35181595
DOI: 10.1523/JNEUROSCI.1008-21.2022 -
Archives of Oral Biology Feb 2013Peripheral treatment with the cholinergic agonist pilocarpine increases salivary gland blood flow and induces intense salivation that is reduced by the central injection...
OBJECTIVE
Peripheral treatment with the cholinergic agonist pilocarpine increases salivary gland blood flow and induces intense salivation that is reduced by the central injection of moxonidine (α2-adrenoceptors/imidazoline agonist). In the present study, we investigated the effects of the intracerebroventricular (i.c.v.) injection of pilocarpine alone or combined with moxonidine also injected i.c.v. On submandibular/sublingual gland (SSG) vascular resistance. In addition, the effects of these treatments on arterial pressure, heart rate and on mesenteric and hindlimb vascular resistance were also tested.
DESIGN
Male Holtzman rats with stainless steel cannula implanted into lateral ventricle and anaesthetized with urethane+α-chloralose were used.
RESULTS
Pilocarpine (500nmol/1μl) injected i.c.v. Reduced SSG vascular resistance and increased arterial pressure, heart rate and mesenteric vascular resistance. Contrary to pilocarpine alone, the combination of moxonidine (20nmol/1μl) and pilocarpine injected i.c.v. Increased SSG vascular resistance, an effect abolished by the pre-treatment with the α2-adrenoceptor antagonist yohimbine (320nmol/2μl). The increase in arterial pressure, heart rate and mesenteric resistance was not modified by the combination of moxonidine and pilocarpine i.c.v.
CONCLUSION
These results suggest that the activation of central α2-adrenoceptors may oppose to the effects of central cholinergic receptor activation in the SSG vascular resistance.
Topics: Animals; Imidazoles; Injections; Male; Pilocarpine; Rats; Receptors, Adrenergic; Salivary Glands; Vascular Resistance; Vasoconstriction; Yohimbine
PubMed: 22818538
DOI: 10.1016/j.archoralbio.2012.06.017 -
Neurobiology of Disease Sep 2022Mesial temporal lobe epilepsy (MTLE) is the most common type of focal refractory epilepsy and is characterized by recurring seizures that are often refractory to...
Mesial temporal lobe epilepsy (MTLE) is the most common type of focal refractory epilepsy and is characterized by recurring seizures that are often refractory to medication. Since parvalbumin-positive (PV) interneurons were recently shown to play significant roles in ictogenesis, we established here how bilateral optogenetic stimulation of these interneurons in the hippocampus CA3 regions modulates seizures, interictal spikes and high-frequency oscillations (HFOs; ripples: 80-200 Hz, fast ripples: 250-500 Hz) in the pilocarpine model of MTLE. Bilateral optogenetic stimulation of CA3 PV-positive interneurons at 8 Hz (lasting 30 s, every 2 min) was implemented in PV-ChR2 mice for 8 consecutive days starting on day 7 (n = 8) or on day 13 (n = 6) after pilocarpine-induced status epilepticus (SE). Seizure occurrence was higher in both day 7 and day 13 groups of PV-ChR2 mice during periods of optogenetic stimulation ("ON"), compared to when stimulation was not performed ("OFF") (day 7 group = p < 0.01, day 13 group = p < 0.01). In the PV-ChR2 day 13 group, rates of seizures (p < 0.05), of interictal spikes associated with fast ripples (p < 0.01), and of isolated fast ripples (p < 0.01) during optogenetic stimulations were significantly higher than in the PV-ChR2 day 7 group. Our findings reveal that bilateral activation of PV-interneurons in the hippocampus (leading to a presumptive increase in GABA signaling) favors ictogenesis. These effects may also mirror the neuropathological changes that occur over time after SE in this animal model.
Topics: Animals; Epilepsy, Temporal Lobe; Mice; Optogenetics; Pilocarpine; Seizures; Status Epilepticus
PubMed: 35718264
DOI: 10.1016/j.nbd.2022.105794 -
The British Journal of Ophthalmology Jan 1974
Review
Topics: Cyclopentanes; Glaucoma; Gonioscopy; Humans; Intraocular Pressure; Iris; Moxisylyte; Phenylephrine; Pilocarpine; Pneumonia, Pneumococcal; Pupil
PubMed: 4276441
DOI: 10.1136/bjo.58.1.41 -
Journal of Neurophysiology May 2018Although convulsive seizures occurring during pilocarpine-induced epileptogenesis have received considerable attention, nonconvulsive seizures have not been closely...
Although convulsive seizures occurring during pilocarpine-induced epileptogenesis have received considerable attention, nonconvulsive seizures have not been closely examined, even though they may reflect the earliest signs of epileptogenesis and potentially guide research on antiepileptogenic interventions. The definition of nonconvulsive seizures based on brain electrical activity alone has been controversial. Here we define and quantify electrographic properties of convulsive and nonconvulsive seizures in the context of the acquired epileptogenesis that occurs after pilocarpine-induced status epilepticus (SE). Lithium-pilocarpine was used to induce the prolonged repetitive seizures characteristic of SE; when SE was terminated with paraldehyde, seizures returned during the 2-day period after pilocarpine treatment. A distinct latent period ranging from several days to >2 wk was then measured with continuous, long-term video-EEG. Nonconvulsive seizures dominated the onset of epileptogenesis and consistently preceded the first convulsive seizures but were still present later. Convulsive and nonconvulsive seizures had similar durations. Postictal depression (background suppression of the EEG) lasted for >100 s after both convulsive and nonconvulsive seizures. Principal component analysis was used to quantify the spectral evolution of electrical activity that characterized both types of spontaneous recurrent seizures. These studies demonstrate that spontaneous nonconvulsive seizures have electrographic properties similar to convulsive seizures and confirm that nonconvulsive seizures link the latent period and the onset of convulsive seizures during post-SE epileptogenesis in an animal model. Nonconvulsive seizures may also reflect the earliest signs of epileptogenesis in human acquired epilepsy, when intervention could be most effective. NEW & NOTEWORTHY Nonconvulsive seizures usually represent the first bona fide seizure following a latent period, dominate the early stages of epileptogenesis, and change in severity in a manner consistent with the progressive nature of epileptogenesis. This analysis demonstrates that nonconvulsive and convulsive seizures have different behavioral outcomes but similar electrographic signatures. Alternatively, epileptiform spike-wave discharges fail to recapitulate several key seizure features and represent a category of electrical activity separate from nonconvulsive seizures in this model.
Topics: Animals; Disease Models, Animal; Electroencephalography; Male; Muscarinic Agonists; Pilocarpine; Rats; Rats, Sprague-Dawley; Seizures; Status Epilepticus; Time Factors
PubMed: 29442558
DOI: 10.1152/jn.00721.2017