CBBS Best Paper of The Year 2020

CBBS-spokesman Prof. Dr. med. Stefan Remy, Prof. Dr. med. Emrah Düzel and Prof. Dr. Toemme Noesselt hand over the certificates and cheques to the award winners. Photos: Rinka/OVGU

A synthetic synaptic organizer protein restores glutamatergic neuronal circuits

Synapses play a central role in the brain’s ability to store and process information. They are junctions through which signals are passed from one nerve cell to the next. A number of specific molecules ensure that synapses are formed and reconfigured whenever necessary. An international team of researchers has now combined various structural elements of such naturally occurring molecules into an artificial protein called CPTX and tested its effect in different models of neurological diseases. The protein was designed to act as a universal bridge builder that links to specific molecules on the surfaces of two contacting cells, and thereby either triggers the formation of new synapses or strengthens already existing ones. The neuroscientists from DZNE Magdeburg found that CPTX improves memory in a mouse model of Alzheimer’s disease and increases the number of synapses and their capacity to change. Further research by the study partners in the UK and Japan revealed that delivery of CPTX to mice with motor dysfunction — caused either by spinal cord injury or pathological conditions similar to cerebellar ataxia — improved the animal’s mobility. At the cellular level, the drug was shown to do even better than some of its natural analogs in building and strengthening nerve connections. Thus, CPTX could be the prototype for a new class of drugs with clinical potential.

Learning in anticipation of reward and punishment: perspectives across the human lifespan

In this study, we examined how action learning across the human lifespan (7-80 years, 247 participants) can be influenced by reward and punishment. Our study revealed important age-related differences between children/adolescents, young, middle-aged and older adults. These differences in learning abilities across the lifespan may be important evolutionary mechanisms, e.g. increased action learning in adolescence necessary to facilitate active exploration and independence into adulthood or alternatively adaptation to maintain decision-making abilities despite declining learning ability in old age. We believe our findings will be of interest to the broader scientific community - from developmental psychologists to researchers investigating the effects of ageing on cognitive decline. Given the importance of lifelong learning and age-appropriate teaching in our ageing society, we believe our work will be of great interest to the general public and an important topic for public outreach.

Sources of path integration error in young and aging humans

Spatial navigation is an important and complex cognitive function, which is often impaired in old age - especially in the course of age-related dementia such as Alzheimer's disease. The ability to navigate an environment comprises multiple different cognitive sub-processes (e.g. sensory perception of stimuli, neuronal processing of spatial information, memory processes, etc.). However, which of these sub-processes are responsible for the age-related decline in navigational performance is largely unknown. For the present study, we developed a novel behavioral task to assess the participants’ navigational ability in virtual reality. Specifically, this task aims at measuring “path integration” performance, which is based on the function of so-called grid cells in the entorhinal cortex, and shows pathological changes already in the earliest stages of Alzheimer's disease. Using a complex mathematical model, we were able to split-up performance on this task into several components to determine the influence of different cognitive sub-processes, and thus identify the main sources of errors during path integration. While it has been previously assumed that path integration errors are mainly caused by specific memory processes (i.e., “memory decay”), our model identified a maladaptive neural noise that accumulates over distance traveled during navigation, and shows that this noise is a major source of error that corrupts positional computations in the human brain's navigation circuit. Moreover, our work demonstrates that this accumulating noise, which likely arises during the neural processing of sensory-perceived spatial information, increases in older age, and accounts for the majority of age-related path integration deficits. Based on this work, it will be possible in the future to develop behavioral tests for clinical diagnostics that can provide early indications of incipient Alzheimer's disease, so that affected patients can be given possible therapy at an earlier disease stage.

Hippocampal vascular reserve associated with cognitive performance and hippocampal volume

Inside the human brain there is a small structure, just a few cubic centimeters in size, which is called the “hippocampus” because its shape resembles a seahorse. Strictly speaking, the hippocampus exists twice: once in each brain hemisphere. It is considered the control center of memory. Damage to the hippocampus, such as it occurs in Alzheimer’s and other brain diseases, is known to impair memory. But what role does blood supply in particular play? A team of scientists headed by Prof. Stefanie Schreiber and Prof. Emrah Düzel, both affiliated to the DZNE and the University Medicine Magdeburg, investigated this question. The researchers used high-resolution magnetic resonance imaging (MRI) to examine the blood supply to the hippocampus of 47 women and men aged 45 to 89 years. The study participants also underwent a neuropsychological test battery, which assessed, in particular, memory and speech. From pathological studies it has been known for some time that the hippocampus is supplied by either one or two arteries. It also happens that only one of the two hippocampi, which occur in every brain, is supplied by two vessels. This varies between individuals. The reasons are unknown. Maybe there is a genetic predisposition. In the cognition tests, those study participants in whom at least one hippocampus was doubly supplied generally scored better. The fact that the blood supply is fundamentally important for the brain is certainly trivial and has been extensively documented. However, the study focused particularly on the hippocampus and a disease of the small brain vessels (cerebral small vessel disease). Little is actually known about this. Of the study subjects, 27 did not manifest signs of brain diseases. The remaining twenty participants showed pathological alterations of small brain blood vessels. In these individuals, sporadic cerebral small vessel disease had been diagnosed prior to the investigations, as Dr. Valentina Perosa explains. She is first author of the current study and currently a postdoctoral research fellow in Boston, USA. These individuals exhibited a broad spectrum of neurological anomalies, including mild cognitive impairment. The healthy subjects generally scored better on cognitive tests than the study participants with small vessel disease. Among the participants with disease, those with at least one hippocampus supplied by two arteries reached better scores in cognition. “Our study shows a clear link between blood supply to the hippocampus and cognitive performance,” says Schreiber, summarizing the results. “This suggests that brain blood flow might play a key role in the declining of memory performance, whether caused by age or disease.” Such findings help to understand disease mechanisms and can also be useful for the development of novel treatment options, as the Neurologist points out.