New chemical trail leads to the secrets of memory and depression

on 21 December 2017
The trouble with the brain

The feelings associated with depression will always be the result of neural processing, a chemical soup that permeates certain brain regions. However, when treating a client, I think it's really important to hear their story because experience tells me that depression is not always the result of dysfunctional neural processing. Sometimes life sucks and that can cause chemical malaise that is described as depression . . . 

The mind is kind, allowing us to believe we are in control!

In the second paragraph, the author says "Almost each one of us lives in the belief that he/she directs his/her mind completely consciously and fully independently." This has not been my experience as a therapist. In fact, I'd say the opposite would be more factual. And although not a sweeping generalisation, "almost each one of us," is pretty close to one! It is the use of generalisations that, I believe, is an integral part of the problem, be it depression, anxiety or stress etc. The overuse of such language (always, never, all the time, constantly etc.) has the potential to distort reality; it certainly is omnipresent in every client (no exaggeration) I have ever treated for these conditions. I would imagine the number of people who make use of generalisations, is vast. However, it is not the use of them that is the problem, sometimes it's convenient to do so. it's the frequency and duration of their use that becomes the problem (too much of a bad thing)!

That said, I really do believe that the more we engage our mind, the easier life becomes but there is a caveat. We have to address the negativity, ambiguity, vagueness and even the duplicity in our language. We also have to be able to clearly define what we want; not so easy to do, maybe; but possible. The brain and mind are genii at working together to produce specific outcomes, sadly we live in a world where there is too much attention paid to the negative, ambiguous, vague and duplicitous (especially our self-talk), maybe leading to the outcome we get but not the one we necessarily hoped for?. However, we can slowly begin to change that dynamic, first by seeking help with understanding and then addressing our demons. Along the way, resolving linguistic anomalies and shifting the mindset to a more positive position. Life, as an experience,  is dependent on how our brain and mind process memories of the past and the associated dialogue that aids their expression. In therapy, it is the ability to reframe, adjust and reconsolidate memory, that ultimately gives each client the opportunity to achieve what feels like a paradigm shift in their mental processing.

But, life can be difficult and depression makes it more so. So, definitely, medications have a part to play in the treatment of depression because they can help each patient become more stabilised and open to therapeutic mind-based interventions. The primary role of medication is to restore normal service. The primary role of Hypnotherapy is to change the way the past expresses itself; change that expression (not the event or the past etc.) and you change your present and your future!

To find out more about my treatment for depression, you can go here:  Help with depression or book an appointment for a Free Consultation here!

The Research: New chemical trail leads to the secrets of memory and depression

The world is bad and life is meaningless? It is not necessarily the fault of the world or life -- or even your willingness. The sources of depression are complex and still poorly understood chemical processes occurring in the brain between neurons. One of them has just been investigated and described by scientists from the Nencki Institute of Experimental Biology in Warsaw. The knowledge gained will be used, among others, in search of new anti-depressants.

Almost every one of us lives in the belief that he/she directs his/her mind completely consciously and fully independently. In fact, many human behaviours, such as addiction or the tendency for depression, are determined by complex physicochemical processes occurring in different brain structures. Particularly important here are the mechanisms that work in synapses, that is in areas where neurons transmit signals. The scientists from the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw, in collaboration with the University College of London, the German Center for Neurodegenerative Diseases and the Hannover Medical School, have just unveiled another secret of the chemical enigma hidden here. For the first time, they described a whole new signal path associated with 5-HT7R, one of the receptors present in dendritic spines within synapses. The results are presented in the well-known biological journal Cell Reports. The editorial office further emphasised the importance of the publication, placing the associated graphics on the cover.

"Synapses are particularly important in communication between neurons, and so in areas where these cells come into contact with their neighbours. Understanding of processes taking place here is still a major challenge of great importance for science and medicine," says Prof. Jakub Wlodarczyk, head of the Laboratory of Cell Biophysics at the Nencki Institute. "Our contribution was to describe the previously unknown signalling pathways, associated with one of the serotonin receptor variants. Knowing this path, we can begin to think, for example, of new ways of chemical control of certain cases of depression."

Man is his/her memory. Deprived of the possibility of preserving our own observations and experiences, we would not be able to associate events, form the personality characteristic only for us, or function socially. We owe remembering and associating to the extraordinary ability of the brain to plastic modelling of the structure of connections between neurons. A key role here is played by processes occurring in synapses, i.e. areas where numerous and branched neuronal processes (dendrites and axons) come into contact with other cells (mostly adjacent neurons). Communication disorders between the neurons are at the root of Parkinson's or Alzheimer's disease and lead to addiction, depression, schizophrenia, autism or epilepsy.

Scientists from the Nencki Institute of Experimental Biology focused their attention on biological processes that occur between the extracellular matrix (the substance that surrounds neurons, containing many different proteins), and dendritic spines, small processes largely covering the dendrites. Contemporary research indicates that both learning and memorisation are related to the number, size and shape of dendritic spines.

"The larger the spine, the more different types of receptors that capture some of the chemical compounds from the environment can be found there. These compounds are secreted by the adjacent neuron to the extracellular matrix in the synaptic cleft and participate in signal transmission. Our group was interested in the processes occurring with the participation of one of the types of serotonin receptors, i.e. the 5-HT7R receptor. Many antipsychotic or antidepressant substances interact directly with this receptor. Furthermore, it has recently been discovered that the pharmacological blocking of this receptor has antidepressant effects," explains PhD Monika Bijata (Nencki Institute), for whom the issues discussed were the basis for her doctoral dissertation.

The research conducted, on the Polish side funded by the HARMONIA grant of the National Science Centre and by the TANGO grant of the National Center for Research and Development, allowed us to determine that when the neurotransmitter activates the 5-HT7R receptor, the extracellular matrix is re-modelled. For the first time, it was demonstrated that the 5-HT7R receptor forms CD44 protein complexes and that the CD44 can be cleaved by the enzyme secreted by the stimulated receptor: the MMP9 metalloprotease. As a result of cutting, another protein, i.e. Cdc42, is activated. It is the one that, through the effect on the actin cytoskeleton, contributes to the growth of the dendritic spine. It has also been proven that the spines enlarged as a result of the operation of the described signalling pathways are indeed functional.

"Now, when we already know the signalling pathways associated with the 5-HT7R receptor activity, it will be easier for us to select molecular targets for new, potentially more effective antidepressant therapies. We can try to block the MMP9 enzyme activity, reduce the CD44 protein cleavage or specifically affect another part of the path," says PhD. Bijata.

"We gained knowledge about the chemical changes in the extracellular matrix that occur during the activation of the 5-HT7R receptor while exploring the neurons. However, it can also be used in relation to some other types of cells, such as cancer cells. This is the way to other therapies, for example, preventing cancers," complements prof. Wlodarczyk.

The experimental part relating to the experiments conducted on animals deprived of the 5-HT7R receptor was performed by PhD Bijata during her scientific internship at the Prof. Evgeni Ponimaskin laboratory from the Hannover Medical School.

The Nencki Institute of Experimental Biology of the Polish Academy of Sciences has been established in 1918 and is the largest non-university centre for biological research in Poland. Priority fields for the Institute include neurobiology, neurophysiology, cellular biology and biochemistry and molecular biology -- at the level of complexity from tissue organisms through cellular organelles to proteins and genes. There are 31 labs at the Institute, among them modern Laboratory of Confocal Microscopy, Laboratory of Cytometry, Laboratory of Electron Microscopy, Behavioural and Electrophysiological Tests. The Institute is equipped with state-of-the-art research equipment and a modernised animal house, where lab animals are bred, also transgenic animals, in accordance with the highest standards. Quality of experiments, publications and close ties with the international science community, place the Institute among the leading biological research centres in Europe.

Story Source: Materials provided by the Nencki Institute of Experimental BiologyNote: Content may be edited for style and length.

Journal Reference: Monika Bijata, Josephine Labus, Daria Guseva, Michał Stawarski, Malte Butzlaff, Joanna Dzwonek, Jenny Schneeberg, Katrin Böhm, Piotr Michaluk, Dmitri A. Rusakov, Alexander Dityatev, Grzegorz Wilczyński, Jakub Wlodarczyk, Evgeni Ponimaskin. Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular MatrixCell Reports, 2017; 19 (9): 1767 DOI: 10.1016/j.celrep.2017.05.023