Current Neuropharmacology - Volume 10, Issue 2, 2012

Neurotransmitters and hormones regulate major immune functions, including the selection of T helper (Th)1 or Th2 cytokine responses, related to cell-mediated and humoral immunity, respectively. A role of imbalance and dynamic switching of Th1/Th2 system has been proposed, with relative displacement of the immune reserve in relation to complex interaction between Th1/Th2 and neuro-hormonal balance fluctuations, in the pathogenesis of various chronic human diseases, probably also including psychiatric disorders. Components of the stress system such as norepinephrine (NE) and glucocorticoids appear to mediate a Th2 shift, while serotonin (5-HT) and melatonin might mediate a Th1 shift. Some antidepressants would occur affecting these systems, acting on neurotransmitter balance (especially the 5-HT/NE balance) and expression levels of receptor subtypes, which in turn affect cytokine production and relative Th1/Th2 balance. It could be therefore hypothesized that the antidepressant-related increase in NE tone enhances the Th2 response, while the decrease in NE tone or the increase in 5-HT tone enhances the Th1 response. However, the neurotransmitter and Th1/Th2 balance modulation could be relative, aiming to restore physiological levels a previous imbalance in receptor sensitivity and cytokine production. The considerations on neuro-immunomodulation could represent an additional aid in the study of pathophysiology of psychiatric disorders and in the choice of specific antidepressants in specific clusters of symptoms, especially in comorbidity with internal pathologies. Furthermore limited data, reviewed here, have shown the effectiveness of some antidepressants as pure immunomodulators. However, these considerations are tentative and require experimental confirmation or refutation by future studies.

In patients with brain tumor (BT), seizures are the onset symptom in 20-40% of patients, while a further 20-45% of patients will present them during the course of the disease. These patients present a complex therapeutic profile and require a unique and multidisciplinary approach. The choice of antiepileptic drugs is challenging for this particular patient population because brain tumor-related epilepsy (BTRE) is often drug-resistant, has a strong impact on the quality of life and weighs heavily on public health expenditures. In BT patients, the presence of epilepsy is considered the most important risk factor for long-term disability. For this reason, the problem of the proper administration of medications and their potential side effects is of great importance, because good seizure control can significantly improve the patient’s psychological and relational sphere. In these patients, new generation drugs such as gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin, topiramate, zonisamide are preferred because they have fewer drug interactions and cause fewer side effects. Among the recently marketed drugs, lacosamide has demonstrated promising results and should be considered a possible treatment option. Therefore, it is necessary to develop a customized treatment plan for each individual patient with BTRE. This requires a vision of patient management concerned not only with medical therapies (pharmacological, surgical, radiological, etc.) but also with emotional and psychological support for the individual as well as his or her family throughout all stages of the illness.

Tetracyclines are a class of antibiotics which could act as neuroprotective molecules in several neurological disorders, such as Huntington disease, Parkinson disease, stroke and multiple sclerosis. The main biological effects of tetracyclines are the inhibition of microglial activation, the attenuation of apoptosis and the suppression of reactive oxygen species production. The anti-apoptotic effect of tetracyclines involves the mitochondrion, and the major target for neuroprotective effects of tetracyclines lies within the complex network that links mitochondria, oxidative stress and apoptosis. Neuromuscular disorders are due to dysfunction of motor neurons, peripheral nerves, neuromuscular junction, or skeletal muscle itself. Animal studies have shown that minocycline could play neuroprotective effects in amyotrophic lateral sclerosis, but these positive findings have not been replicated in patients. Other neuromuscular disorders which tetracyclines may benefit are Guillain-Barre syndrome and other neuropathies, muscular dystrophies and mitochondrial disorders. However, well-designed double-blind controlled trials are still needed. Further studies are strongly needed to establish the most appropriate timing and dosage, as well as the indications for which tetracyclines could be effective and safe. Here, we review the neuroprotective effects of tetracyclines in animal models, the clinical studies in humans, and we focus on their potential application in patients with neuromuscular disorders.

The evolution in the understanding of the neurobiology of most prevalent mental disorders such as major depressive disorder (MDD), bipolar disorder or schizophrenia has not gone hand in hand with the synthesis and clinical use of new drugs that would represent a therapeutic revolution such as that brought about by selective serotonin reuptake inhibitors (SSRIs) or atypical antipsychotics. Although scientists are still a long way from understanding its true aetiology, the neurobiological concept of depression has evolved from receptor regulation disorder, to a neurodegenerative disorder with a hippocampal volume decrease with the controversial reduction in neurotrophins such as BDNF, to current hypotheses that consider depression to be an inflammatory and neuroprogressive process. As regards antidepressants, although researchers are still far from knowing their true mechanism of action, they have gone from monoaminergic hypotheses, in which serotonin was the main protagonist, to emphasising the anti-inflammatory action of some of these drugs, or the participation of p11 protein in their mechanism of action. In the same way, according to the inflammatory hypothesis of depression, it has been proposed that some NSAIDS such as aspirin or drugs like simvastatin that have an anti-inflammatory action could be useful in some depressive patients. Despite the fact that there may be some data to support their clinical use, common sense and the evidence advise us to use already tested protocols and wait for the future to undertake new therapeutic strategies.

In recent years, a growing interest has been dedicated to the study of the endocannabinoid system. The isolation of Cannabis sativa main psychotropic compound, Δ9-tetrahydrocannabinol (THC), has led to the discovery of an atypical neurotransmission system that modulates the release of other neurotransmitters and participates in many biological processes, including the cascade of inflammatory responses. In this context, cannabinoids have been studied for their possible therapeutic properties in neuroinflammatory diseases. In this review, historic and biochemical aspects of cannabinoids are discussed, as well as their function as modulators of inflammatory processes and therapeutic perspectives for neurodegenerative disorders, particularly, multiple sclerosis.

The intensity of pain sensation exhibits marked day and night variations. Since the intensity of pain perception is low during dark hours of the night when melatonin levels are high, this hormone has been implicated as one of the prime antinociceptive substances. A number of studies have examined the antinociceptive role of melatonin in acute, inflammatory and neuropathic pain animal models. It has been demonstrated that melatonin exerts antinociceptive actions by acting at both spinal cord and supraspinal levels. The mechanism of antinociceptive actions of melatonin involves opioid, benzodiazepine, α1- and α2-adrenergic, serotonergic and cholinergic receptors. Most importantly however, the involvement of MT1/MT2 melatonergic receptors in the spinal cord has been well documented as an antinociceptive mechanism in a number of animal models of pain perception. Exogenous melatonin has been used effectively in the management of pain in medical conditions such as fibromyalgia, irritable bowel syndrome and migraine and cluster headache. Melatonin has been tried during surgical operating conditions and has been shown to enhance both preoperative and post-operative analgesia. The present review discusses the available evidence indicating that melatonin, acting through MT1/MT2 melatonin receptors, plays an important role in the pathophysiological mechanism of pain.

Due to an overlook on the author's side, the name of the first author in the article entitled as “Aquaporin and Blood Brain Barrier” by Francesca Bonomini, Rezzani R, published in the journal Current Neuropharmacology, 2010, Vol. 8, Issue no. 2, was wrong. The correct name is as follows...

Due to an overlook on the author's side, author’s name in the article entitled as “Aquaporin biology and nervous system” by, Buffoli B published in the journal “Current Neuropharmacology” Vol. 8, Issue no. 2, was wrong. The correct name is as follows: Buffoli B. Aquaporin biology and nervous system. Curr Neuropharmacol 2010, 8(2), 97-104.