The nucleus locus coeruleus modulatory effect on memory formation: A literature review

The nucleus locus coeruleus (LC), the main source of norepinephrine in the brain, is connected to memory processing regions such as the hippocampus and baso-lateral amygdala (BLA). The LC and its mostly associated noradrenergic projections, play an important role in memory formation parallel to other neurotransmitter systems. It has been suggested that the unique response characteristics of LC to various situations strengthens different memories formation. Here, we review key related findings of LC effect on memory (avoidance, spatial, cognitive) formation, memory processing regions, memory molecular mechanisms as well as its role in memory related disorders. Literature review was conducted by extensive search on ISI, PubMed and Scopus, online databases from May 2021 to July 2021. According to the obtained results, LC noradrenergic projections to memory processing areas of the brain, can modulate the encoding, consolidation, and retrieval for different memory types. Also, the LC regulates neurogenesis and neural plasticity in different areas of the brain. Evidences suggested that dysfunction of the LC and its associated noradrenergic system may lead to cognitive impairment or a variety of memory-related disorders, including Alzheimer's disease. Finally, it can be concluded that the locus coeruleus noradrenergic system may be a suitable target for the treatment of different memory/cognitive disorders

Lateral habenula deep brain stimulation alleviates depression-like behaviors and reverses the oscillatory pattern in the nucleus accumbens in an animal model of depression

Depression is a series of symptoms that influence mood, thinking, and behavior and create unpleasant emotions like hopelessness and apathy. Treatment-resistant depression (TRD) affects 30 % of depression patients despite the availability of several non-invasive therapies. Deep brain stimulation (DBS) is a novel therapy for TRD. The aim of the current study was to evaluate the effect of LHb-DBS by recording local field potentials (LFP) and conducting behavioral experiments.Thirty-two mature male Wistar rats were randomly divided into four groups: control, chronic mild stress (CMS), CMS+DBS, and DBS. After surgery and electrode placement in the lateral habenula (LHb), nucleus accumbens (NAc), and prelimbic cortex (PrL), the CMS protocol was applied for 3 weeks to create depression-like models. The open field test (OFT), sucrose preference test (SPT), and forced swim test (FST) were also performed. In the DBS groups, the LHb area was stimulated for four consecutive days. Finally, on the 22nd day, LFP was recorded from the NAc and PrL and analyzed using MATLAB software. Analyzing the findings using ANOVA and P-values ≤ 0.05 was considered.LHb-DBS alleviated depression-like behaviors in chronic moderate stress model rats (P ≤ 0.05). Three weeks of CMS enhanced almost all band powers in the NAc, while LHb-DBS decreased the power of the theta, alpha, beta, and gamma bands in the NAc (P ≤ 0.05), and the low-gamma band in the PrL. CMS also boosted the NAc-PrL coherence in low-frequency bands, while LHb-DBS increased beta and low gamma band coherence (P ≤ 0.05).In sum, the results of the present study showed that depression enhances low-frequency coherence between NAc and PrL cortex. Depression also potentiates many brain oscillations in the NAc, which can be mainly reversed by LHb-DBS

Palmitoylethanolamide attenuates PTZ-induced seizures through CB1 and CB2 receptors

Epilepsy is one of the most common neurologic disorders. Though there are effective medications available to reduce the symptoms of the disease, their side effects have limited their usage. Palmitoylethanolamide (PEA) has been shown to attenuate seizure in different animal models. The objective of the current study was to evaluate the role of CB1 and CB2 receptors in this attenuation. Male wistar rats were used for the current experiment. PTZ was injected to induce chemical kindling in animals. After verification of kindling in animals, treatment was performed with PEA, AM251 and AM630 in different groups. Latency to induce seizure, seizure stages and latency and duration of fifth stage of seizure was recorded for each animal. Injection of PTZ led to seizure in the animals. Pretreatment with PEA increased the latency to initiate seizures and reduced the duration of seizure. Pretreatment with different dosages of AM251 had contrary effects so that at lower doses they increased the seizure in animals but at higher doses led to the attenuation of seizure. AM630 increased seizures in a dose dependent manner. Combination of the antagonists increased the seizure parameters and attenuated the effect of PEA on seizure. PEA attenuated the PTZ-induced seizures and pretreatment with CB1 and CB2 antagonists diminished this effect of PEA, but still PEA was effective, which might be attributed to the contribution of other receptors in PEA anti-epileptic properties. Findings of the current study implied that endocannabinoid signaling pathway might have an important role in the effects of PEA

Essential role of hippocampal noradrenaline in the regulation of spatial working memory and TDP-43 tissue pathology

8noExtensive loss of noradrenaline-containing neurons and fibers is a nearly invariant feature of Alzheimer’s Disease (AD). However, the exact noradrenergic contribution to cognitive and histo- pathological changes in AD is still unclear. Here, this issue was addressed following selective lesioning and intrahippocampal implantation of embryonic noradrenergic progenitors in developing rats. Starting from about 3 months and up to 12 months post-surgery, animals underwent behav- ioral tests to evaluate sensory-motor, as well as spatial learning and memory, followed by post- mortem morphometric analyses. At 9 months, Control, Lesioned and Lesion1Transplant animals exhibited equally efficient sensory-motor and reference memory performance. Interestingly, working memory abilities were seen severely impaired in Lesion-only rats and fully recovered in Transplanted rats, and appeared partly lost again 2 months after ablation of the implanted neuroblasts. Morphological analyses confirmed the almost total lesion-induced noradrenergic neuronal and terminal fiber loss, the near-normal reinnervation of the hippocampus promoted by the transplants, and its complete removal by the second lesion. Notably, the noradrenergic-rich transplants normalized also the nuclear expression of the transactive response DNA-binding protein 43 (TDP- 43) in various hippocampal subregions, whose cytoplasmic (i.e., pathological) occurrence appeared dramatically increased as a result of the lesions. Thus, integrity of ascending noradrenergic inputs to the hippocampus may be required for the regulation of specific aspects of learning and memory and to prevent TDP-43 tissue pathology.reservedmixedPintus, Roberta; Riggi, Margherita; Cannarozzo, Cecilia; Valeri, Andrea; de Leo, Gioacchino; Romano, Maurizio; Gulino, Rosario; Leanza, GiampieroPintus, Roberta; Riggi, Margherita; Cannarozzo, Cecilia; Valeri, Andrea; de LEO, Gioacchino; Romano, Maurizio; Gulino, Rosario; Leanza, Giampier