Victor Bancila

Nicotine-induced and depolarisation-induced glutamate release from hippocampus mossy fibre synaptosomes: two distinct mechanisms

Hippocampus mossy fibre terminals activate CA3 pyramidal neurons via two distinct mechanisms, both quantal and glutamatergic: (i) rapid excitatory transmission in response to afferent action potentials and (ii) delayed and prolonged release following nicotinic receptor activation. These processes were analysed here using rat hippocampus mossy fibres synaptosomes. The relationships between synaptosome depolarisation and glutamate release were established in response to high‐KCl and gramicidin challenges. Half‐maximal release corresponded to a 52 mV depolarisation step. KCl‐induced release was accompanied by transient dissipation of the proton gradient across synaptic vesicle membrane. Nicotine elicited a substantial glutamate release from mossy fibre synaptosomes (EC50 3.14 μM; Vmax 12.01 ± 2.1 nmol glutamate/mg protein; Hill’s coefficient 0.99). However, nicotine‐induced glutamate release was not accompanied by any change in the membrane potential or in the vesicular proton gradient. The effects of acetylcholine (200 μM) were similar to those of nicotine (25 μM). Nicotinic α7 receptors were evidenced by immuno‐cytochemistry on the mossy fibre synaptosome plasma membrane. Therefore, the same terminals can release glutamate in response to two distinct stimuli: (i) rapid neurotransmission involving depolarisation‐induced activation of voltage‐gated Ca2+ channels and (ii) a slower nicotinic activation which does not involve depolarisation or dissipation of the vesicular proton gradient.

Comorbidity between attention deficit hyperactivity disorder (ADHD) and bipolar disorder in a specialized mood disorders outpatient clinic

BACKGROUND Comorbidity between ADHD and Bipolar Disorder (BD) is associated with greater severity of BD. The current study aims at investigating, in a specialized mood disorders clinic, the percentage of comorbid ADHD-BD subjects and assessing the impact of ADHD on the severity of BD. METHODS Out of 539 mood disorders subjects, the medical records of 138 BD subjects were scrutinized in terms of their clinical and demographic characteristics, and their scores at the Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist were logged. Those positively scoring at the ASRS-v1.1 underwent clinical assessment by a senior psychiatrist specialized in ADHD. Comorbid ADHD-BD subjects were then compared with BD sufferers without ADHD. RESULTS Sixty-three (45.65%) of the participants were screened positive at the ASRS-v1.1. 49 were clinically assessed for the presence of ADHD. Only 27 (55%) received a diagnosis of ADHD. Comorbid ADHD-BD subjects were found to be younger at the onset of BD, showed higher numbers of depressive episodes, more anxiety and substance use disorders, more borderline personality traits and greater cyclothymic temperament. Comorbid BD-ADHD subjects reported more childhood emotional abuse. LIMITATIONS Some subjects were unreachable and thus not clinically assessed for ADHD. CONCLUSIONS More than 20% of BD subjects were suffering from ADHD. The comorbidity of the two disorders was associated with worse outcomes, possibly resulting from stressful early-life events. More than 40% of the subjects who scored positively at the ASRS-v1.1 did not suffer from ADHD, which suggests that this scale should be used with caution in BD subjects.

Reconstitution of mediatophore-supported quantal acetylcholine release

Synaptic transmission of a nerve impulse is an extremely rapid event relying on transfer of brief chemical impulses from one cell to another. This transmission is dependent upon Ca2+ and known to be quantal, which led to the widely accepted vesicular hypothesis of neurotransmitter release. However, at least in the case of rapid synaptic transmission the hypothesis has been found difficult to reconcile with a number of observations. In the article, we shall review data from experiments dealing with reconstitution of quantal and Ca2+-dependent acetylcholine release in: i) proteoliposomes, ii)Xenopus oocytes, and iii) release-deficient cell lines. In these three experimental models, release is dependent on the expression of the mediatophore, a protein isolated from the plasma membrane of cholinergic nerve terminals of theTorpedo electric organ. We shall discuss the role of mediatophore in quantal acetylcholine release, its possible involvement in morphological changes affecting presynaptic membrane during the release, and its interactions with others proteins of the cholinergic nerve terminal.

Ultra-Fast Versus Sustained Cholinergic Transmission: A Variety of Different Mechanisms

Although synaptic transmission was assumed to use the same mechanisms in the case of different synapses of the central and peripheral nervous system, recent research revealed a great variety of different processes. Time might be a crucial factor to be considered in this diversity. It is recalled that the speed of a chemical reaction is inversely related to affinity. “Time is gained at the expense of sensitivity” as noticed by Bernard Katz (1989). Therefore, synaptic transmission will occur at a high speed only if it is supported by low affinity reactions. In the present work, we compare two examples of ultra-rapid transmission (the Torpedo nerve electroplaque synapse and the rat hippocampus mossy fiber/CA3 synapses), with a cholinergic process operating with high affinity but at a low speed: the release of glutamate elicited by nicotine from mossy fibers of the rat hippocampus.

You don't believe in a patient's depression? Watch the watch!

Depressive states may at times be particularly tricky to ascertain or confirm during a time-limited consultation. For example, a patient may present with what has been termed as smiling depression. We present the case of a female patient with bipolar II disorder whose difficult-to-ascertain depression could be confirmed by her automatic wristwatch, which regularly stopped when she was hypokinetic as a result of her depression.